<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03751657</url>
  </required_header>
  <id_info>
    <org_study_id>NN1436-4383</org_study_id>
    <secondary_id>U1111-1208-4124</secondary_id>
    <secondary_id>2018-000322-63</secondary_id>
    <nct_id>NCT03751657</nct_id>
  </id_info>
  <brief_title>A Research Study to Compare Insulin 287 Once a Week to Insulin Glargine (100 Units/mL) Once a Day in People With Type 2 Diabetes.</brief_title>
  <official_title>An Investigational Trial Comparing the Efficacy and Safety of Once Weekly NNC0148-0287 C (Insulin 287) Versus Once Daily Insulin Glargine, Both in Combination With Metformin, With or Without DPP-4 Inhibitors, in Insulin naïve Subjects With Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novo Nordisk A/S</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novo Nordisk A/S</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study compares 2 medicines for people with type 2 diabetes: insulin 287 (a new medicine)&#xD;
      and insulin glargine (a medicine doctors can already prescribe). The study doctors will test&#xD;
      insulin 287 to see how well it works compared to insulin glargine. The study will also test&#xD;
      if insulin 287 is safe. The study participants will either get insulin 287 or insulin&#xD;
      glargine (100 units/mL) - which treatment the participants get is decided by chance. The&#xD;
      participants will need to inject their selves every day about the same time. Once a week the&#xD;
      participant will need to take 1 extra injection on the same day of the week. The participants&#xD;
      will have 16 clinic visits and 14 phone calls with the study doctor. During the study, the&#xD;
      doctors will ask you to: 1) measure your blood sugar every day with a blood glucose meter&#xD;
      using a finger prick, 2) write down different information in a paper diary daily and return&#xD;
      this to your doctor, 3) wear a medical device to measure your blood sugar all the time for 2&#xD;
      weeks 5 times during the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 29, 2018</start_date>
  <completion_date type="Actual">January 17, 2020</completion_date>
  <primary_completion_date type="Actual">December 16, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Sponsor staff involved in the clinical trial is masked according to company standard procedures.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]</measure>
    <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
    <description>Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in HbA1c [Millimoles/Mole (mmol/Mol)]</measure>
    <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
    <description>Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Fasting Plasma Glucose</measure>
    <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
    <description>Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>9-point Profile (Individual SMPG Values)</measure>
    <time_frame>Week 26 (Visit 28)</time_frame>
    <description>Participants measured their plasma glucose (PG) levels using blood glucose meters (as plasma equivalent values of capillary whole blood glucose) at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values after 26 weeks are presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time</measure>
    <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
    <description>Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).</measure>
    <time_frame>Week 26 (Visit 28)</time_frame>
    <description>Participants measured their plasma glucose (PG) levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Presented fluctuation in 9-point SMPG profile is the integrated absolute distance from the mean profile value divided by measurement time and is calculated using the trapezoidal method. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting C-peptide</measure>
    <time_frame>At week 26 (Visit 28)</time_frame>
    <description>Fasting C-peptide at week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Body Weight</measure>
    <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
    <description>Change in body weight from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine</measure>
    <time_frame>week 25 (Visit 27) and 26 (Visit 28)</time_frame>
    <description>Weekly dose of insulin 287 and weekly dose of glargine at week 25 and week 26 are presented.The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Treatment Emergent Adverse Events (TEAEs)</measure>
    <time_frame>From baseline (Visit 2) to week 31 (Visit 30)</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and &lt;3.9 mmol/L (≥54 and &lt;70 mg/dL), Confirmed by BG Meter)</measure>
    <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
    <description>Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy with plasma glucose value of equal to or above (&gt;=) 3.0 and less than (&lt;) 3.9 mmol/L (&gt;= 54 and &lt; 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occurred from week 0 to week 26 are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (&lt;3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)</measure>
    <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
    <description>Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (&lt;) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occurred from week 0 to week 26 are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Severe Hypoglycaemic Episodes (Level 3)</measure>
    <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
    <description>Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred from week 0 to week 26 are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Anti-insulin 287 Antibody Titres</measure>
    <time_frame>From baseline (Visit 2) to week 31 (Visit 30)</time_frame>
    <description>Samples from the insulin 287 arm of the study were analysed for anti-insulin 287 antibodies. Confirmed anti-insulin 287 antibody positive samples had an antibody titre value determined. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)</measure>
    <time_frame>From baseline (Visit 2) to week 31 (Visit 30)</time_frame>
    <description>Anti-insulin 287 or glargine antibodies were classified as negative if % B/T was below a certain cut point. Samples positive for anti-insulin 287 or glargine antibodies were further tested for cross-reactivity to endogenous insulin. Samples not further tested are categorised as not applicable (NA). Unknown refers to samples with insufficient volume to perform analysis. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Anti-insulin 287 Antibody Level</measure>
    <time_frame>From baseline (Visit 2) to week 31 (Visit 30)</time_frame>
    <description>Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels. The results for change in anti-insulin 287 antibody titres are reported as a separate endpoint.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">247</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Insulin 287</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive once weekly insulin 287 and once daily placebo in combination with metformin with or without dipeptidyl peptidase-4 inhibitors (DPP4i) during 26 weeks of treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Insulin glargine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive once daily insulin glargine and once weekly placebo in combination with metformin with or without DPP4i during 26 weeks of treatment period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin icodec</intervention_name>
    <description>Insulin 287 once weekly subcutaneous (s.c.) injections at the starting dose of 70 units. Dose adjustment was done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL)</description>
    <arm_group_label>Insulin 287</arm_group_label>
    <other_name>Insulin 287</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (insulin 287)</intervention_name>
    <description>Participants will receive once weekly s.c. injections of placebo equivalent to insulin 287.</description>
    <arm_group_label>Insulin glargine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose.</description>
    <arm_group_label>Insulin 287</arm_group_label>
    <arm_group_label>Insulin glargine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dipeptidyl peptidase-4 inhibitors</intervention_name>
    <description>Dipeptidyl peptidase-4 inhibitors are considered as non investigational medicinal products. Subject will continue dipeptidyl peptidase-4 inhibitor at stable pre-trial dose.</description>
    <arm_group_label>Insulin 287</arm_group_label>
    <arm_group_label>Insulin glargine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin glargine</intervention_name>
    <description>Insulin glargine (100 U/mL) once daily s.c. injections at the starting dose of 10 units. Dose adjustment will be done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL).</description>
    <arm_group_label>Insulin glargine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (insulin glargine)</intervention_name>
    <description>Participants will receive once daily s.c. injections of placebo equivalent to insulin glargine.</description>
    <arm_group_label>Insulin 287</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, aged 18-75 years (both inclusive) at the time of signing informed&#xD;
             consent&#xD;
&#xD;
          -  Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the&#xD;
             day of screening&#xD;
&#xD;
          -  HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory&#xD;
&#xD;
          -  Stable daily dose(s) for 90 days prior to the day of screening of any of the following&#xD;
             antidiabetic drug(s) or combination regime(s): Any metformin formulations greater than&#xD;
             or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's&#xD;
             medical record) OR Any metformin formulations greater than or equal to 1500 mg or&#xD;
             maximum tolerated or effective dose (as documented in subject medical record) with&#xD;
             Dipeptidyl peptidase-4 inhibitor (DPP4i) (greater than or equal to half of the maximum&#xD;
             approved dose according to local label or maximum tolerated or effective dose (as&#xD;
             documented in subject's medical records)&#xD;
&#xD;
          -  Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to&#xD;
             the day of screening is allowed, as is prior insulin treatment for gestational&#xD;
             diabetes&#xD;
&#xD;
          -  Body mass index (BMI) less than or equal to 40.0 kg/m^2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of&#xD;
             screening and between screening and randomisation&#xD;
&#xD;
          -  Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or&#xD;
             transient ischaemic attack within 180 days prior to the day of screening and between&#xD;
             screening and randomisation&#xD;
&#xD;
          -  Presently classified as being in New York Heart Association (NYHA) Class IV&#xD;
&#xD;
          -  Treatment with any medication for the indication of diabetes or obesity other than&#xD;
             stated in the inclusion criteria within the past 90 days prior to the day of&#xD;
             screening. However, short term insulin treatment for a maximum of 14 days prior to the&#xD;
             day of screening is allowed, as is prior insulin treatment for gestational diabetes&#xD;
&#xD;
          -  Anticipated initiation or change in concomitant medications (for more than 14&#xD;
             consecutive days) known to affect weight or glucose metabolism (e.g. treatment with&#xD;
             orlistat, thyroid hormones, or corticosteroids)&#xD;
&#xD;
          -  Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by&#xD;
             a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist&#xD;
             or another suitably qualified health care provider within the past 90 days prior to&#xD;
             screening or in the period between screening and randomisation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Reporting Anchor and Disclosure (1452)</last_name>
    <role>Study Director</role>
    <affiliation>Novo Nordisk A/S</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lancaster</city>
        <state>California</state>
        <zip>93534</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Ventura</city>
        <state>California</state>
        <zip>93003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Walnut Creek</city>
        <state>California</state>
        <zip>94598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Roswell</city>
        <state>Georgia</state>
        <zip>30076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28277</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Whiteville</city>
        <state>North Carolina</state>
        <zip>28472</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37411</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-9302</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Renton</city>
        <state>Washington</state>
        <zip>98057</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 1V7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Brampton</city>
        <state>Ontario</state>
        <zip>L6S 0C6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Concord</city>
        <state>Ontario</state>
        <zip>L4K 4M2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Etobicoke</city>
        <state>Ontario</state>
        <zip>M9R 4E1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8M 1K7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Sarnia</city>
        <state>Ontario</state>
        <zip>N7T 4X3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>St-Marc-des-Carrières</city>
        <state>Quebec</state>
        <zip>G0A 4B0</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Brno</city>
        <zip>62500</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Pardubice</city>
        <zip>530 02</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Praha 1</city>
        <zip>110 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Praha 4</city>
        <zip>149 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Praha 5</city>
        <zip>150 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Praha 8</city>
        <zip>181 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Praha</city>
        <zip>128 08</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Rakovník</city>
        <zip>269 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Slaný</city>
        <zip>27401</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Athens</city>
        <zip>115 25</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Athens</city>
        <zip>GR-11527</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Thessaloniki</city>
        <zip>GR-54636</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Thessaloniki</city>
        <zip>GR-54642</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Thessaloniki</city>
        <zip>GR-57010</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bialystok</city>
        <zip>15-404</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Gdansk</city>
        <zip>80-546</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lodz</city>
        <zip>90-132</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Poznan</city>
        <zip>61-251</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Warsaw</city>
        <zip>00-465</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Wierzchoslawice</city>
        <zip>33-122</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bratislava</city>
        <zip>821 02</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bratislava</city>
        <zip>851 01</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kosice</city>
        <zip>040 01</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Moldava nad Bodvou</city>
        <zip>045 01</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Sahy</city>
        <zip>93601</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Trencin</city>
        <zip>91101</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Koper</city>
        <zip>SI-6000</zip>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Ljubljana</city>
        <zip>SI-1000</zip>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Greece</country>
    <country>Poland</country>
    <country>Slovakia</country>
    <country>Slovenia</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Rosenstock J, Bajaj HS, Janež A, Silver R, Begtrup K, Hansen MV, Jia T, Goldenberg R. Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment. PMID:32960514</citation>
  </results_reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <results_first_submitted>December 11, 2020</results_first_submitted>
  <results_first_submitted_qc>January 28, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 1, 2021</results_first_posted>
  <last_update_submitted>March 5, 2021</last_update_submitted>
  <last_update_submitted_qc>March 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Insulin Glargine</mesh_term>
    <mesh_term>Dipeptidyl-Peptidase IV Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>According to the Novo Nordisk disclosure commitment on novonordisk-trials.com</ipd_description>
    <ipd_url>http://novonordisk-trials.com</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 29, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT03751657/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 29, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT03751657/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The trial was conducted at 49 sites in Canada (7), Czech Republic (9), Greece (5), Poland (6), Slovakia (6),Slovenia (2) and United States (14). One site in the United States screened, but didn't randomise any participant.</recruitment_details>
      <pre_assignment_details>Insulin-naïve participants with Type 2 Diabetes (T2D) inadequately controlled on metformin with or without dipeptidyl peptidase 4 inhibitor (DPP4i) were randomized in a 1:1 manner to receive once weekly insulin 287 and once daily placebo or once weekly placebo and once daily insulin glargine subcutaneously (s.c).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Insulin 287</title>
          <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
        </group>
        <group group_id="P2">
          <title>Insulin Glargine</title>
          <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="125"/>
                <participants group_id="P2" count="122"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="122"/>
                <participants group_id="P2" count="119"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full analysis set (FAS) included all randomised participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Insulin 287</title>
          <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
        </group>
        <group group_id="B2">
          <title>Insulin Glargine</title>
          <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="125"/>
            <count group_id="B2" value="122"/>
            <count group_id="B3" value="247"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.7" spread="8.2"/>
                    <measurement group_id="B2" value="59.4" spread="9.5"/>
                    <measurement group_id="B3" value="59.6" spread="8.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="108"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="69"/>
                    <measurement group_id="B3" value="139"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="115"/>
                    <measurement group_id="B2" value="116"/>
                    <measurement group_id="B3" value="231"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="109"/>
                    <measurement group_id="B2" value="113"/>
                    <measurement group_id="B3" value="222"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]</title>
        <description>Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
        <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
        <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]</title>
          <description>Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
          <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
          <units>Percentage point of HbA1c</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="120"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.33" spread="0.07"/>
                    <measurement group_id="O2" value="-1.15" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The response and change from baseline in response after 26 weeks are analysed using a linear mixed model for repeated measures (MMRM) with an unstructured covariance matrix and treatment, region, use of DPP-4 inhibitor and visit as fixed factors, and baseline response as covariate. Furthermore, the model includes the interaction between visit and all explanatory variables.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0818</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Treatment difference</param_type>
            <param_value>-0.18</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.38</ci_lower_limit>
            <ci_upper_limit>0.02</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Fasting Plasma Glucose</title>
        <description>Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
        <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
        <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Fasting Plasma Glucose</title>
          <description>Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
          <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
          <units>mmol/l</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="121"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.20" spread="0.16"/>
                    <measurement group_id="O2" value="-2.99" spread="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>9-point Profile (Individual SMPG Values)</title>
        <description>Participants measured their plasma glucose (PG) levels using blood glucose meters (as plasma equivalent values of capillary whole blood glucose) at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values after 26 weeks are presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
        <time_frame>Week 26 (Visit 28)</time_frame>
        <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>9-point Profile (Individual SMPG Values)</title>
          <description>Participants measured their plasma glucose (PG) levels using blood glucose meters (as plasma equivalent values of capillary whole blood glucose) at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values after 26 weeks are presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
          <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
          <units>mmol/l</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Before breakfast</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="109"/>
                    <count group_id="O2" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.70" spread="0.19"/>
                    <measurement group_id="O2" value="6.19" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes after start of breakfast</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                    <count group_id="O2" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.90" spread="0.19"/>
                    <measurement group_id="O2" value="8.51" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Before lunch</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="109"/>
                    <count group_id="O2" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.09" spread="0.19"/>
                    <measurement group_id="O2" value="6.19" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes after start of lunch</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                    <count group_id="O2" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.83" spread="0.19"/>
                    <measurement group_id="O2" value="8.50" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Before main evening meal</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                    <count group_id="O2" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.55" spread="0.19"/>
                    <measurement group_id="O2" value="6.96" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes after the start of main evening meal</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.01" spread="0.19"/>
                    <measurement group_id="O2" value="8.47" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Before bedtime</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.35" spread="0.19"/>
                    <measurement group_id="O2" value="7.87" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At 4:00 a.m.</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                    <count group_id="O2" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.72" spread="0.19"/>
                    <measurement group_id="O2" value="5.98" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Before breakfast the following day</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="109"/>
                    <count group_id="O2" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.74" spread="0.19"/>
                    <measurement group_id="O2" value="6.05" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time</title>
        <description>Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
        <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
        <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time</title>
          <description>Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
          <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
          <units>mmol/l</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.70" spread="0.12"/>
                    <measurement group_id="O2" value="-2.26" spread="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).</title>
        <description>Participants measured their plasma glucose (PG) levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Presented fluctuation in 9-point SMPG profile is the integrated absolute distance from the mean profile value divided by measurement time and is calculated using the trapezoidal method. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
        <time_frame>Week 26 (Visit 28)</time_frame>
        <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).</title>
          <description>Participants measured their plasma glucose (PG) levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Presented fluctuation in 9-point SMPG profile is the integrated absolute distance from the mean profile value divided by measurement time and is calculated using the trapezoidal method. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
          <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
          <units>mmol/l</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.92" lower_limit="0.84" upper_limit="1.01"/>
                    <measurement group_id="O2" value="0.94" lower_limit="0.86" upper_limit="1.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fasting C-peptide</title>
        <description>Fasting C-peptide at week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
        <time_frame>At week 26 (Visit 28)</time_frame>
        <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Fasting C-peptide</title>
          <description>Fasting C-peptide at week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
          <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
          <units>Nanomoles per liter (nmol/l)</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="115"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.44" lower_limit="0.40" upper_limit="0.48"/>
                    <measurement group_id="O2" value="0.47" lower_limit="0.43" upper_limit="0.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Body Weight</title>
        <description>Change in body weight from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
        <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
        <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Body Weight</title>
          <description>Change in body weight from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
          <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
          <units>Kilogram</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.49" spread="0.36"/>
                    <measurement group_id="O2" value="1.56" spread="0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine</title>
        <description>Weekly dose of insulin 287 and weekly dose of glargine at week 25 and week 26 are presented.The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
        <time_frame>week 25 (Visit 27) and 26 (Visit 28)</time_frame>
        <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine</title>
          <description>Weekly dose of insulin 287 and weekly dose of glargine at week 25 and week 26 are presented.The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
          <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
          <units>Units of Insulin</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="120"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="229.06" lower_limit="205.08" upper_limit="255.83"/>
                    <measurement group_id="O2" value="284.05" lower_limit="253.97" upper_limit="317.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Treatment Emergent Adverse Events (TEAEs)</title>
        <description>An adverse event (AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.</description>
        <time_frame>From baseline (Visit 2) to week 31 (Visit 30)</time_frame>
        <population>The safety analysis set (SAS) included all participants who received at least one dose of the investigational product or comparator.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment Emergent Adverse Events (TEAEs)</title>
          <description>An adverse event (AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.</description>
          <population>The safety analysis set (SAS) included all participants who received at least one dose of the investigational product or comparator.</population>
          <units>Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="229"/>
                    <measurement group_id="O2" value="158"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and &lt;3.9 mmol/L (≥54 and &lt;70 mg/dL), Confirmed by BG Meter)</title>
        <description>Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy with plasma glucose value of equal to or above (&gt;=) 3.0 and less than (&lt;) 3.9 mmol/L (&gt;= 54 and &lt; 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occurred from week 0 to week 26 are presented.</description>
        <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
        <population>SAS included all participants who received at least one dose of the investigational product or comparator.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and &lt;3.9 mmol/L (≥54 and &lt;70 mg/dL), Confirmed by BG Meter)</title>
          <description>Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy with plasma glucose value of equal to or above (&gt;=) 3.0 and less than (&lt;) 3.9 mmol/L (&gt;= 54 and &lt; 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occurred from week 0 to week 26 are presented.</description>
          <population>SAS included all participants who received at least one dose of the investigational product or comparator.</population>
          <units>Episodes</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="358"/>
                    <measurement group_id="O2" value="145"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (&lt;3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)</title>
        <description>Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (&lt;) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occurred from week 0 to week 26 are presented.</description>
        <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
        <population>SAS included all participants who received at least one dose of the investigational product or comparator.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (&lt;3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)</title>
          <description>Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (&lt;) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occurred from week 0 to week 26 are presented.</description>
          <population>SAS included all participants who received at least one dose of the investigational product or comparator.</population>
          <units>Episodes</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                    <measurement group_id="O2" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Severe Hypoglycaemic Episodes (Level 3)</title>
        <description>Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred from week 0 to week 26 are presented.</description>
        <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
        <population>SAS included all participants who received at least one dose of the investigational product or comparator.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Severe Hypoglycaemic Episodes (Level 3)</title>
          <description>Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred from week 0 to week 26 are presented.</description>
          <population>SAS included all participants who received at least one dose of the investigational product or comparator.</population>
          <units>Episodes</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Anti-insulin 287 Antibody Titres</title>
        <description>Samples from the insulin 287 arm of the study were analysed for anti-insulin 287 antibodies. Confirmed anti-insulin 287 antibody positive samples had an antibody titre value determined. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.</description>
        <time_frame>From baseline (Visit 2) to week 31 (Visit 30)</time_frame>
        <population>SAS included all participants who received at least one dose of the investigational product or comparator. Overall number of participants analysed = Number of participants contributing to the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Anti-insulin 287 Antibody Titres</title>
          <description>Samples from the insulin 287 arm of the study were analysed for anti-insulin 287 antibodies. Confirmed anti-insulin 287 antibody positive samples had an antibody titre value determined. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.</description>
          <population>SAS included all participants who received at least one dose of the investigational product or comparator. Overall number of participants analysed = Number of participants contributing to the analysis.</population>
          <units>Antibody titers</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="979.9" spread="3177.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)</title>
        <description>Anti-insulin 287 or glargine antibodies were classified as negative if % B/T was below a certain cut point. Samples positive for anti-insulin 287 or glargine antibodies were further tested for cross-reactivity to endogenous insulin. Samples not further tested are categorised as not applicable (NA). Unknown refers to samples with insufficient volume to perform analysis. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.</description>
        <time_frame>From baseline (Visit 2) to week 31 (Visit 30)</time_frame>
        <population>SAS included all participants who received at least one dose of the investigational product or comparator.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)</title>
          <description>Anti-insulin 287 or glargine antibodies were classified as negative if % B/T was below a certain cut point. Samples positive for anti-insulin 287 or glargine antibodies were further tested for cross-reactivity to endogenous insulin. Samples not further tested are categorised as not applicable (NA). Unknown refers to samples with insufficient volume to perform analysis. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.</description>
          <population>SAS included all participants who received at least one dose of the investigational product or comparator.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="125"/>
                    <count group_id="O2" value="122"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Negative</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Positive</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Applicable</title>
                  <measurement_list>
                    <measurement group_id="O1" value="124"/>
                    <measurement group_id="O2" value="112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 31</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="120"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Negative</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Positive</title>
                  <measurement_list>
                    <measurement group_id="O1" value="86"/>
                    <measurement group_id="O2" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Applicable</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in HbA1c [Millimoles/Mole (mmol/Mol)]</title>
        <description>Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
        <time_frame>From baseline (Visit 2) to week 26 (Visit 28)</time_frame>
        <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in HbA1c [Millimoles/Mole (mmol/Mol)]</title>
          <description>Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.</description>
          <population>FAS included all randomised participants. &quot;Number of Participants Analyzed&quot; = Number of participants contributing to the analysis.</population>
          <units>mmol/mol</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="120"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.51" spread="0.79"/>
                    <measurement group_id="O2" value="-12.54" spread="0.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The response and change from baseline in response after 26 weeks are analysed using a linear MMRM with an unstructured covariance matrix and treatment, region, use of DPP-4 inhibitor and visit as fixed factors, and baseline response as covariate.Furthermore, the model includes the interaction between visit and all explanatory variables.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0818</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Treatment difference</param_type>
            <param_value>-1.97</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.19</ci_lower_limit>
            <ci_upper_limit>0.25</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Anti-insulin 287 Antibody Level</title>
        <description>Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels. The results for change in anti-insulin 287 antibody titres are reported as a separate endpoint.</description>
        <time_frame>From baseline (Visit 2) to week 31 (Visit 30)</time_frame>
        <population>Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin 287</title>
            <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Anti-insulin 287 Antibody Level</title>
          <description>Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels. The results for change in anti-insulin 287 antibody titres are reported as a separate endpoint.</description>
          <population>Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Week 0 to Week 31 Results are based on the SAS which included all participants who received at least one dose of Insulin 287 or Insulin glargine. The SAS included all participants who received at least one dose of the investigational product or comparator.</time_frame>
      <desc>A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.</desc>
      <group_list>
        <group group_id="E1">
          <title>Insulin 287</title>
          <description>Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and &gt;7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
        </group>
        <group group_id="E2">
          <title>Insulin Glargine</title>
          <description>Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: &lt; 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and &gt;7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="122"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatosplenomegaly</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Emphysematous pyelonephritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Lower limb fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
              <event>
                <sub_title>Azotaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Metrorrhagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 22</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="12" subjects_affected="10" subjects_at_risk="125"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="122"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="125"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="31" subjects_affected="14" subjects_at_risk="125"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="122"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Reporting Anchor and Disclosure (1452)</name_or_title>
      <organization>Novo Nordisk A/S</organization>
      <phone>(+1)866-867-7178</phone>
      <email>clinicaltrials@novonordisk.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03751657
org study id: NN1436-4383
secondary id: U1111-1208-4124
secondary id: 2018-000322-63
nct id: NCT03751657
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The study compares 2 medicines for people with type 2 diabetes: insulin 287 (a new medicine)
      and insulin glargine (a medicine doctors can already prescribe). The study doctors will test
      insulin 287 to see how well it works compared to insulin glargine. The study will also test
      if insulin 287 is safe. The study participants will either get insulin 287 or insulin
      glargine (100 units/mL) - which treatment the participants get is decided by chance. The
      participants will need to inject their selves every day about the same time. Once a week the
      participant will need to take 1 extra injection on the same day of the week. The participants
      will have 16 clinic visits and 14 phone calls with the study doctor. During the study, the
      doctors will ask you to: 1) measure your blood sugar every day with a blood glucose meter
      using a finger prick, 2) write down different information in a paper diary daily and return
      this to your doctor, 3) wear a medical device to measure your blood sugar all the time for 2
      weeks 5 times during the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Sponsor staff involved in the clinical trial is masked according to company standard procedures.
measure: Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]
time frame: From baseline (Visit 2) to week 26 (Visit 28)
description: Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
measure: Change in HbA1c [Millimoles/Mole (mmol/Mol)]
time frame: From baseline (Visit 2) to week 26 (Visit 28)
description: Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
measure: Change in Fasting Plasma Glucose
time frame: From baseline (Visit 2) to week 26 (Visit 28)
description: Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
measure: 9-point Profile (Individual SMPG Values)
time frame: Week 26 (Visit 28)
description: Participants measured their plasma glucose (PG) levels using blood glucose meters (as plasma equivalent values of capillary whole blood glucose) at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values after 26 weeks are presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
measure: Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time
time frame: From baseline (Visit 2) to week 26 (Visit 28)
description: Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
measure: Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).
time frame: Week 26 (Visit 28)
description: Participants measured their plasma glucose (PG) levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Presented fluctuation in 9-point SMPG profile is the integrated absolute distance from the mean profile value divided by measurement time and is calculated using the trapezoidal method. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
measure: Fasting C-peptide
time frame: At week 26 (Visit 28)
description: Fasting C-peptide at week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
measure: Change in Body Weight
time frame: From baseline (Visit 2) to week 26 (Visit 28)
description: Change in body weight from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
measure: Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine
time frame: week 25 (Visit 27) and 26 (Visit 28)
description: Weekly dose of insulin 287 and weekly dose of glargine at week 25 and week 26 are presented.The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
measure: Number of Treatment Emergent Adverse Events (TEAEs)
time frame: From baseline (Visit 2) to week 31 (Visit 30)
description: An adverse event (AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.
measure: Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter)
time frame: From baseline (Visit 2) to week 26 (Visit 28)
description: Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy with plasma glucose value of equal to or above (>=) 3.0 and less than (<) 3.9 mmol/L (>= 54 and < 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occurred from week 0 to week 26 are presented.
measure: Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)
time frame: From baseline (Visit 2) to week 26 (Visit 28)
description: Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occurred from week 0 to week 26 are presented.
measure: Number of Severe Hypoglycaemic Episodes (Level 3)
time frame: From baseline (Visit 2) to week 26 (Visit 28)
description: Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred from week 0 to week 26 are presented.
measure: Change in Anti-insulin 287 Antibody Titres
time frame: From baseline (Visit 2) to week 31 (Visit 30)
description: Samples from the insulin 287 arm of the study were analysed for anti-insulin 287 antibodies. Confirmed anti-insulin 287 antibody positive samples had an antibody titre value determined. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.
measure: Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)
time frame: From baseline (Visit 2) to week 31 (Visit 30)
description: Anti-insulin 287 or glargine antibodies were classified as negative if % B/T was below a certain cut point. Samples positive for anti-insulin 287 or glargine antibodies were further tested for cross-reactivity to endogenous insulin. Samples not further tested are categorised as not applicable (NA). Unknown refers to samples with insufficient volume to perform analysis. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.
measure: Change in Anti-insulin 287 Antibody Level
time frame: From baseline (Visit 2) to week 31 (Visit 30)
description: Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels. The results for change in anti-insulin 287 antibody titres are reported as a separate endpoint.
arm group label: Insulin 287
arm group type: Experimental
description: Participants will receive once weekly insulin 287 and once daily placebo in combination with metformin with or without dipeptidyl peptidase-4 inhibitors (DPP4i) during 26 weeks of treatment period.
arm group label: Insulin glargine
arm group type: Active Comparator
description: Participants will receive once daily insulin glargine and once weekly placebo in combination with metformin with or without DPP4i during 26 weeks of treatment period.
intervention type: Drug
intervention name: Insulin icodec
description: Insulin 287 once weekly subcutaneous (s.c.) injections at the starting dose of 70 units. Dose adjustment was done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL)
arm group label: Insulin 287
other name: Insulin 287
intervention type: Drug
intervention name: Placebo (insulin 287)
description: Participants will receive once weekly s.c. injections of placebo equivalent to insulin 287.
arm group label: Insulin glargine
intervention type: Drug
intervention name: Metformin
description: Metformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose.
arm group label: Insulin 287
arm group label: Insulin glargine
intervention type: Drug
intervention name: Dipeptidyl peptidase-4 inhibitors
description: Dipeptidyl peptidase-4 inhibitors are considered as non investigational medicinal products. Subject will continue dipeptidyl peptidase-4 inhibitor at stable pre-trial dose.
arm group label: Insulin 287
arm group label: Insulin glargine
intervention type: Drug
intervention name: Insulin glargine
description: Insulin glargine (100 U/mL) once daily s.c. injections at the starting dose of 10 units. Dose adjustment will be done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL).
arm group label: Insulin glargine
intervention type: Drug
intervention name: Placebo (insulin glargine)
description: Participants will receive once daily s.c. injections of placebo equivalent to insulin glargine.
arm group label: Insulin 287
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Clinical Reporting Anchor and Disclosure (1452)
role: Study Director
affiliation: Novo Nordisk A/S
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country: Canada
country: Czechia
country: Greece
country: Poland
country: Slovakia
country: Slovenia
country: United States
citation: Rosenstock J, Bajaj HS, Janež A, Silver R, Begtrup K, Hansen MV, Jia T, Goldenberg R. Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment. PMID:32960514
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Metformin
mesh term: Insulin Glargine
mesh term: Dipeptidyl-Peptidase IV Inhibitors
sharing ipd: Yes
ipd description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
ipd url: http://novonordisk-trials.com
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 