<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/NCT03819790</url>
  </required_header>
  <id_info>
    <org_study_id>VARIATION 2 SA</org_study_id>
    <nct_id>NCT03819790</nct_id>
  </id_info>
  <brief_title>The Effect of Soliqua on Glucose Variability in Type 2 Patients Among South Asians</brief_title>
  <acronym>VARIATION 2 SA</acronym>
  <official_title>Variability of Glucose Assessed in a Randomized Trial Comparing the Initiation of A Treatment Approach With Biosimilar Basal Insulin Analog Or a Titratable iGlarLixi combinatioN in Type 2 Diabetes Among South Asian Subjects (VARIATION 2 SA Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LMC Diabetes &amp; Endocrinology Ltd.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>LMC Diabetes &amp; Endocrinology Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall objective of this study is to compare the effects of Soliqua, a titratable&#xD;
      combination of insulin and GLP-1 receptor agonist in a single pen versus Glargine U100&#xD;
      insulin (Basaglar or Lantus) and gliclazide MR, both added to metformin, on measures of&#xD;
      glucose variability using masked CGM data among people of South Asian origin living in Canada&#xD;
      with type 2 diabetes (T2DM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The VARIATION 2 SA study is a prospective, open-label, randomized controlled, multi-centre&#xD;
      trial to compare the efficacy of two insulin initiation approaches (Soliqua vs Glargine U100&#xD;
      insulin (Basaglar or Lantus) + gliclazide MR) added to maximum tolerated metformin on glucose&#xD;
      variability (using masked CGM) in South Asians with T2DM who will initiate insulin therapy&#xD;
      with HbA1c of 7.1-11% (inclusive). After giving informed consent and being assessed by&#xD;
      eligibility, the patient will stop other oral hypoglycemic agents except metformin (SGLT2&#xD;
      inhibitor may be continued if the patient has cardiovascular diseases history) and enter a&#xD;
      1-week run-in phase with Basaglar or Lantus insulin. During this week (considered as&#xD;
      baseline), the patient will: 1) be administered Basaglar or Lantus insulin at an initial dose&#xD;
      of 10 units in the morning and increase 1 U/day if fasting glucose &gt;5.5 mmol/L; 2) complete 2&#xD;
      questionnaires to assess the patient-reported outcomes (PROs); 3) wear a masked continuous&#xD;
      glucose monitor (CGM) to assess glucose variability; 4) record carbohydrate intake for at&#xD;
      least 3 consecutive days. If a patient demonstrates good adherence to Basaglar or Lantus&#xD;
      insulin therapy, proper CGM wearing and proper record of carbohydrate intake, and is willing&#xD;
      to adhere to insulin treatment will be randomly assigned (1:1) to receive either Soliqua or&#xD;
      Glargine U100 insulin (Basaglar or Lantus) + gliclazide MR treatment. The patients will&#xD;
      initiate insulin Soliqua or Basaglar/Lantus at their end-of run-in phase insulin dose&#xD;
      (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate&#xD;
      by 1 U/day until fasting glucose reaches 4-5.5 mmol/L. In the next 12 weeks, the patients&#xD;
      will be optimized their insulin doses via clinic visits or phone calls. They will also be&#xD;
      instructed to record their daily fasting glucose, insulin dose, hypoglycemic episodes and any&#xD;
      adverse events in a logbook. The primary outcome is to compare the difference of average&#xD;
      percentage of Time in Range (4.0-10.0 mmol/L) within 24 hours over the CGM period between two&#xD;
      treatments at week 13 after randomization. The co-primary is to compare the difference&#xD;
      average percentage of Time in Range (4.0-10.0 mmol/L) within 12 hours (6 AM- 6 PM) over the&#xD;
      CGM period between two treatments at week 13 after randomization. The secondary outcomes&#xD;
      include the differences on other measurements of glucose variability and patient-reported&#xD;
      outcomes (PROs).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2, 2018</start_date>
  <completion_date type="Actual">November 19, 2019</completion_date>
  <primary_completion_date type="Actual">November 19, 2019</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>Patients will be randomized into either of two arms by an interactive system in a 1:1 ratio. Randomization will be stratified based on the use of sodium-glucose co-transporter-2 (SGLT2) inhibitors.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time in range at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Time with CGM glucose between 4.0 - 10.0 mmol/L within 24 hours over the 7-day CGM period at week 13 after randomization</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time in range within 12-hours (6 AM -6 PM) at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Time with CGM glucose between 4.0 - 10.0 mmol/L within 12-hours (6 AM -6 PM) over the 7-day CGM period at week 13 after randomization</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Daily glucose standard deviation (SD) at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Daily SD of CGM glucose over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall SD of CGM glucose at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Overall SD of CGM glucose over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean of glucose at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Mean of CGM glucose over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of hypoglycemia at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Number of hypoglycemic event which is defined as CGM glucose &lt;4.0 mmol/L for at least 15 mins (3 consecutive CGM readings) over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in hypoglycemia at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Time with CGM glucose &lt; 4.0 mmol/L over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of hyperglycemia at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Number of hyperglycemic event which is defined as CGM glucose &gt;10.0 mmol/L at least 15 mins (3 consecutive CGM readings) over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in hyperglycemia at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Time with CGM glucose &gt;10.0 mmol/L over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily glucose standard deviation (SD) within 12 hours (6AM-6PM) at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Daily SD of CGM glucose within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall SD of glucose within 12 hours (6AM-6PM) at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Overall SD of CGM glucose within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean of glucose within 12 hours (6AM-6PM) at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Mean of CGM glucose within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of hypoglycemia within 12 hours (6AM-6PM) at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Number of hypoglycemic event which is defined as CGM glucose &lt;4.0 mmol/L for at least 15 mins (3 consecutive CGM readings) within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in hypoglycemia within 12 hours (6AM-6PM) at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Time with CGM glucose &lt;4.0 mmol/L within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of hyperglycemia within 12 hours (6AM-6PM) at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Number of hypoglycemic event which is defined as CGM glucose &gt;10.0 mmol/L for at least 15 mins (3 consecutive CGM readings) within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in hyperglycemia within 12 hours (6AM-6PM) at week 13</measure>
    <time_frame>7 days</time_frame>
    <description>Time with CGM glucose &gt;10.0 mmol/L within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A1C mean at week 13</measure>
    <time_frame>Week 13</time_frame>
    <description>Average of A1C at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes A1C</measure>
    <time_frame>15 weeks</time_frame>
    <description>A1C value at Visit10 at 13 weeks after randomization minus A1C value at Visit 1 at week -2 (2 weeks before randomization)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of A1C &lt;7% at week 13</measure>
    <time_frame>Week 13</time_frame>
    <description>the number of patients who have A1C &lt;7% divided by the total number of patients who have A1C measurement at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of A1C &lt;8% at week 13</measure>
    <time_frame>Week 13</time_frame>
    <description>the number of patients who have A1C &lt;8% divided by the total number of patients who have A1C measurement at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean basal insulin dose at week 13</measure>
    <time_frame>Week 13</time_frame>
    <description>Average of basal insulin dose from patients' diary at week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in weight</measure>
    <time_frame>15 weeks</time_frame>
    <description>Weight difference between week 13 after randomization and baseline at week -2 (2 weeks before randomization) = weight at Visit 10 at week 13 - weight at Visit 1 at week -2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in waist circumference</measure>
    <time_frame>15 weeks</time_frame>
    <description>Waist circumference change between week 13 after randomization and baseline at week -2 (2 week before randomization)= waist circumference at Visit 10 at week 13- waist circumference at Visit 1 at week -2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in carbohydrate intake</measure>
    <time_frame>14 weeks</time_frame>
    <description>Carbohydrate intake change between week 13 after randomization and baseline at week -1 = carbohydrate intake at Visit 10 at week 13 - carbohydrate intake at Visit 2 at week -1 (1 week before randomization)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who have A1C ≤ 7% with no hypoglycemia and no weight gain from baseline</measure>
    <time_frame>Week 13</time_frame>
    <description>the number of patients who have A1C ≤ 7% with no hypoglycemia and no weight gain from baseline divided by the total number of patients at Week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who have A1C ≤ 7% with no hypoglycemia and weight gain &lt;3% from baseline</measure>
    <time_frame>Week 13</time_frame>
    <description>the number of patients who have A1C ≤ 7% with no hypoglycemia and weight gain &lt;3% from baseline divided by the total number of patients at Week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who have fasting blood glucose ≤ 5.5 mmol/L without nocturnal hypoglycemia</measure>
    <time_frame>Week 13</time_frame>
    <description>the number of patients who have fasting blood glucose ≤ 5.5 mmol/L without nocturnal hypoglycemia divided by the total number of patients at Week 13 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in DiabMedSat Score</measure>
    <time_frame>14 weeks</time_frame>
    <description>DiabMedSat Score will be generated using Diabetes Medication Satisfaction (DiabMedSat) questionnaire. It measures the levels of the subjects' satisfaction with their diabetes medication(s). The range of the score is 0 to 100. The higher the score, the greater the satisfaction. The changes in the score will measure the score difference between Visit 10 at week 13 after randomization and Visit 2 at week -1 (1 week before randomization)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HFS Score</measure>
    <time_frame>14 weeks</time_frame>
    <description>HFS Score will be measured by the Hypoglycemia Fear Survey which assesses the subject's behaviors to avoid hypoglycemia and to measure the subjects' worries about hypoglycemia and its consequences in the past 3 months. The range of the score will be 0 to 132. The higher the score, the greater the fear.&#xD;
The changes will be the score difference between Visit 10 at week 13 after randomization and Visit 2 at week -1 (1 week before randomization).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HCP treatment satisfaction score</measure>
    <time_frame>Week 13</time_frame>
    <description>HCP treatment satisfaction score will be generated from Healthcare Provider treatment satisfaction questionnaire. It measures the levels of satisfaction of physicians in this study when prescribing this medication at Visit 10 at week 13 after randomization. The range is 0 to 15. The higher the score, the greater the satisfaction.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">119</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Insulin Glargine + GLP-1 RA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Insulin Soliqua (a titratable combination of insulin Glargine + GLP-1 RA) will be administered at the subject's end-of run-in phase insulin dose (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate by one unit per day until fasting glucose level of 4-5.5 mmol/L is obtained, with or without metformin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Basaglar/Lantus + gliclazide MR</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Basal insulin Basaglar/Lantus will be administered at the subject's end-of run-in phase insulin dose (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate by one unit per day until fasting glucose level of 4-5.5 mmol/L is obtained, with gliclazide MR 60 mg OD, with or without metformin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Basal insulin glargine and lixisenatide</intervention_name>
    <description>Soliqua (insulin glargine and lixisenatide): a titratable combination of long-acting basal insulin glargine and lixisenatide (Glucagon-like peptide-1 receptor agonist)</description>
    <arm_group_label>Insulin Glargine + GLP-1 RA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Basal insulin Basaglar/Lantus + gliclazide MR</intervention_name>
    <description>basal long-acting insulin Basaglar/Lantus with gliclazide MR 60 mg OD</description>
    <arm_group_label>Basaglar/Lantus + gliclazide MR</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Patients can be administered with most tolerant dose of metformin</description>
    <arm_group_label>Basaglar/Lantus + gliclazide MR</arm_group_label>
    <arm_group_label>Insulin Glargine + GLP-1 RA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female adults with clinical diagnosis of T2DM diagnosed at least 1 year&#xD;
             before screening and in stable health as assessed by investigator&#xD;
&#xD;
          -  Age between 18 and 80 years (inclusive)&#xD;
&#xD;
          -  Body mass index (BMI) between 20-40 kg/m2 (inclusive)&#xD;
&#xD;
          -  South Asian origin including Afghanistani, Bangladeshi, Indian, Nepali, Pakistani and&#xD;
             Sri Lankan. This includes those patients who identify themselves as South Asian origin&#xD;
             because their ancestors moved from South Asian to another country (e.g. Caribbean&#xD;
             islands, Fiji, etc.)&#xD;
&#xD;
          -  A1C in range of 7.1-11% (inclusive)&#xD;
&#xD;
          -  Fasting glucose on self-monitoring of blood glucose (SMBG) or laboratory testing &lt; 15&#xD;
             mmol/L within the last 30 days&#xD;
&#xD;
          -  Insulin naïve, uncontrolled on oral hypoglycemic medications&#xD;
&#xD;
          -  Kidney function assessment with eGFR &gt;30 mL/min/1.73 m2&#xD;
&#xD;
          -  Written informed consent obtained&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of insulin use (except emergency short-term use defined as less than 12 weeks&#xD;
             for acute illness, hospitalization, pregnancy or with steroid use)&#xD;
&#xD;
          -  Use of GLP-1 receptor agonist in the past 3 months&#xD;
&#xD;
          -  Previous discontinuation of a GLP-1 receptor agonist due to safety, tolerability or&#xD;
             lack of efficacy&#xD;
&#xD;
          -  Pregnant or anticipating pregnancy&#xD;
&#xD;
          -  Current use of steroid&#xD;
&#xD;
          -  Currently on any supervised, intensive, weight-loss dietary or exercise program&#xD;
&#xD;
          -  History of gastroparesis with moderate or higher severity&#xD;
&#xD;
          -  History of pancreatitis&#xD;
&#xD;
          -  Amylase and /or lipase more than three times the upper limit of normal or calcitonin ≥&#xD;
             20 pg/mL (5.9 pmol/L)&#xD;
&#xD;
          -  Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia&#xD;
             (MEN) syndrome&#xD;
&#xD;
          -  Allergic reaction to insulin secretagogues&#xD;
&#xD;
          -  History of weight loss surgery (bariatric bypass surgery or gastric banding)&#xD;
&#xD;
          -  Inability to check SMBG or wear CGM&#xD;
&#xD;
          -  History of severe liver disease or alcohol abuse&#xD;
&#xD;
          -  Severe hypoglycemic reaction (defined as third-party or ambulance assistance or&#xD;
             emergency department visit) within the last 3 months before screening visit&#xD;
&#xD;
          -  Night-shift workers&#xD;
&#xD;
          -  Patients who are recommended to achieve relaxed targets of A1C up to 8.5% by Diabetes&#xD;
             Canada 2018 clinical practice guidelines&#xD;
&#xD;
          -  Current enrollment in another intervention study&#xD;
&#xD;
          -  Patients who miss ≥1 injections of Basaglar/Lantus or discontinue the CGM device or&#xD;
             can not record carbohydrate intake correctly during the run-in phase&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>LMC Brampton</name>
      <address>
        <city>Brampton</city>
        <state>Ontario</state>
        <zip>L6S 0C9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LMC Etobicoke</name>
      <address>
        <city>Etobicoke</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LMC Scarborough</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M1R 0B1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
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    <PMID>24731666</PMID>
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    <PMID>15111485</PMID>
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    <PMID>9449682</PMID>
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  <reference>
    <citation>Leiter LA, Nauck MA. Efficacy and Safety of GLP-1 Receptor Agonists Across the Spectrum of Type 2 Diabetes Mellitus. Exp Clin Endocrinol Diabetes. 2017 Jul;125(7):419-435. doi: 10.1055/s-0043-103969. Epub 2017 Jul 19. German.</citation>
    <PMID>28724168</PMID>
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  <reference>
    <citation>Zaccardi F, Htike ZZ, Webb DR, Khunti K, Davies MJ. Benefits and Harms of Once-Weekly Glucagon-like Peptide-1 Receptor Agonist Treatments: A Systematic Review and Network Meta-analysis. Ann Intern Med. 2016 Jan 19;164(2):102-13. doi: 10.7326/M15-1432. Epub 2015 Dec 8.</citation>
    <PMID>26642233</PMID>
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  <reference>
    <citation>Rosenstock J, Fonseca VA, Gross JL, Ratner RE, Ahren B, Chow FC, Yang F, Miller D, Johnson SL, Stewart MW, Leiter LA; Harmony 6 Study Group. Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro. Diabetes Care. 2014 Aug;37(8):2317-25. doi: 10.2337/dc14-0001. Epub 2014 Jun 4.</citation>
    <PMID>24898300</PMID>
  </reference>
  <reference>
    <citation>Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH; 4B Study Group. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2763-73. doi: 10.2337/dc14-0876. Epub 2014 Jul 10.</citation>
    <PMID>25011946</PMID>
  </reference>
  <reference>
    <citation>Writing Group for the DCCT/EDIC Research Group; Orchard TJ, Nathan DM, Zinman B, Cleary P, Brillon D, Backlund JY, Lachin JM. Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality. JAMA. 2015 Jan 6;313(1):45-53. doi: 10.1001/jama.2014.16107.</citation>
    <PMID>25562265</PMID>
  </reference>
  <reference>
    <citation>Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10.</citation>
    <PMID>18784090</PMID>
  </reference>
  <reference>
    <citation>Lind M, Svensson AM, Kosiborod M, Gudbjornsdottir S, Pivodic A, Wedel H, Dahlqvist S, Clements M, Rosengren A. Glycemic control and excess mortality in type 1 diabetes. N Engl J Med. 2014 Nov 20;371(21):1972-82. doi: 10.1056/NEJMoa1408214.</citation>
    <PMID>25409370</PMID>
  </reference>
  <reference>
    <citation>Esposito K, Giugliano D, Nappo F, Marfella R; Campanian Postprandial Hyperglycemia Study Group. Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation. 2004 Jul 13;110(2):214-9. doi: 10.1161/01.CIR.0000134501.57864.66. Epub 2004 Jun 14.</citation>
    <PMID>15197140</PMID>
  </reference>
  <reference>
    <citation>Kilpatrick ES, Rigby AS, Atkin SL. A1C variability and the risk of microvascular complications in type 1 diabetes: data from the Diabetes Control and Complications Trial. Diabetes Care. 2008 Nov;31(11):2198-202. doi: 10.2337/dc08-0864. Epub 2008 Jul 23.</citation>
    <PMID>18650371</PMID>
  </reference>
  <reference>
    <citation>Bajaj HS, Venn K, Ye C, Patrick A, Kalra S, Khandwala H, Aslam N, Twum-Barima D, Aronson R. Lowest Glucose Variability and Hypoglycemia Are Observed With the Combination of a GLP-1 Receptor Agonist and Basal Insulin (VARIATION Study). Diabetes Care. 2017 Feb;40(2):194-200. doi: 10.2337/dc16-1582. Epub 2016 Dec 2.</citation>
    <PMID>27913575</PMID>
  </reference>
  <reference>
    <citation>Chiu M, Austin PC, Manuel DG, Tu JV. Comparison of cardiovascular risk profiles among ethnic groups using population health surveys between 1996 and 2007. CMAJ. 2010 May 18;182(8):E301-10. doi: 10.1503/cmaj.091676. Epub 2010 Apr 19.</citation>
    <PMID>20403888</PMID>
  </reference>
  <reference>
    <citation>Chiu M, Maclagan LC, Tu JV, Shah BR. Temporal trends in cardiovascular disease risk factors among white, South Asian, Chinese and black groups in Ontario, Canada, 2001 to 2012: a population-based study. BMJ Open. 2015 Aug 10;5(8):e007232. doi: 10.1136/bmjopen-2014-007232.</citation>
    <PMID>26260346</PMID>
  </reference>
  <reference>
    <citation>Gujral UP, Pradeepa R, Weber MB, Narayan KM, Mohan V. Type 2 diabetes in South Asians: similarities and differences with white Caucasian and other populations. Ann N Y Acad Sci. 2013 Apr;1281(1):51-63. doi: 10.1111/j.1749-6632.2012.06838.x. Epub 2013 Jan 14.</citation>
    <PMID>23317344</PMID>
  </reference>
  <reference>
    <citation>Yale JF, Berard L, Groleau M, Javadi P, Stewart J, Harris SB. TITRATION: A Randomized Study to Assess 2 Treatment Algorithms with New Insulin Glargine 300 units/mL. Can J Diabetes. 2017 Oct;41(5):478-484. doi: 10.1016/j.jcjd.2017.06.007. Epub 2017 Aug 10.</citation>
    <PMID>28803820</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>September 24, 2018</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>February 24, 2021</last_update_submitted>
  <last_update_submitted_qc>February 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes, type 2</keyword>
  <keyword>GLP-1 RA</keyword>
  <keyword>Insulin glargine</keyword>
  <keyword>Glucose variability</keyword>
  <keyword>Insulin Titration</keyword>
  <keyword>South Asians</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Lixisenatide</mesh_term>
    <mesh_term>Gliclazide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03819790
org study id: VARIATION 2 SA
nct id: NCT03819790
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The overall objective of this study is to compare the effects of Soliqua, a titratable
      combination of insulin and GLP-1 receptor agonist in a single pen versus Glargine U100
      insulin (Basaglar or Lantus) and gliclazide MR, both added to metformin, on measures of
      glucose variability using masked CGM data among people of South Asian origin living in Canada
      with type 2 diabetes (T2DM).
The VARIATION 2 SA study is a prospective, open-label, randomized controlled, multi-centre
      trial to compare the efficacy of two insulin initiation approaches (Soliqua vs Glargine U100
      insulin (Basaglar or Lantus) + gliclazide MR) added to maximum tolerated metformin on glucose
      variability (using masked CGM) in South Asians with T2DM who will initiate insulin therapy
      with HbA1c of 7.1-11% (inclusive). After giving informed consent and being assessed by
      eligibility, the patient will stop other oral hypoglycemic agents except metformin (SGLT2
      inhibitor may be continued if the patient has cardiovascular diseases history) and enter a
      1-week run-in phase with Basaglar or Lantus insulin. During this week (considered as
      baseline), the patient will: 1) be administered Basaglar or Lantus insulin at an initial dose
      of 10 units in the morning and increase 1 U/day if fasting glucose >5.5 mmol/L; 2) complete 2
      questionnaires to assess the patient-reported outcomes (PROs); 3) wear a masked continuous
      glucose monitor (CGM) to assess glucose variability; 4) record carbohydrate intake for at
      least 3 consecutive days. If a patient demonstrates good adherence to Basaglar or Lantus
      insulin therapy, proper CGM wearing and proper record of carbohydrate intake, and is willing
      to adhere to insulin treatment will be randomly assigned (1:1) to receive either Soliqua or
      Glargine U100 insulin (Basaglar or Lantus) + gliclazide MR treatment. The patients will
      initiate insulin Soliqua or Basaglar/Lantus at their end-of run-in phase insulin dose
      (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate
      by 1 U/day until fasting glucose reaches 4-5.5 mmol/L. In the next 12 weeks, the patients
      will be optimized their insulin doses via clinic visits or phone calls. They will also be
      instructed to record their daily fasting glucose, insulin dose, hypoglycemic episodes and any
      adverse events in a logbook. The primary outcome is to compare the difference of average
      percentage of Time in Range (4.0-10.0 mmol/L) within 24 hours over the CGM period between two
      treatments at week 13 after randomization. The co-primary is to compare the difference
      average percentage of Time in Range (4.0-10.0 mmol/L) within 12 hours (6 AM- 6 PM) over the
      CGM period between two treatments at week 13 after randomization. The secondary outcomes
      include the differences on other measurements of glucose variability and patient-reported
      outcomes (PROs).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be randomized into either of two arms by an interactive system in a 1:1 ratio. Randomization will be stratified based on the use of sodium-glucose co-transporter-2 (SGLT2) inhibitors.
primary purpose: Treatment
masking: None (Open Label)
measure: Time in range at week 13
time frame: 7 days
description: Time with CGM glucose between 4.0 - 10.0 mmol/L within 24 hours over the 7-day CGM period at week 13 after randomization
measure: Time in range within 12-hours (6 AM -6 PM) at week 13
time frame: 7 days
description: Time with CGM glucose between 4.0 - 10.0 mmol/L within 12-hours (6 AM -6 PM) over the 7-day CGM period at week 13 after randomization
measure: Daily glucose standard deviation (SD) at week 13
time frame: 7 days
description: Daily SD of CGM glucose over the 7-day CGM period at week 13 after randomization
measure: Overall SD of CGM glucose at week 13
time frame: 7 days
description: Overall SD of CGM glucose over the 7-day CGM period at week 13 after randomization
measure: Mean of glucose at week 13
time frame: 7 days
description: Mean of CGM glucose over the 7-day CGM period at week 13 after randomization
measure: Frequency of hypoglycemia at week 13
time frame: 7 days
description: Number of hypoglycemic event which is defined as CGM glucose <4.0 mmol/L for at least 15 mins (3 consecutive CGM readings) over the 7-day CGM period at week 13 after randomization
measure: Time in hypoglycemia at week 13
time frame: 7 days
description: Time with CGM glucose < 4.0 mmol/L over the 7-day CGM period at week 13 after randomization
measure: Frequency of hyperglycemia at week 13
time frame: 7 days
description: Number of hyperglycemic event which is defined as CGM glucose >10.0 mmol/L at least 15 mins (3 consecutive CGM readings) over the 7-day CGM period at week 13 after randomization
measure: Time in hyperglycemia at week 13
time frame: 7 days
description: Time with CGM glucose >10.0 mmol/L over the 7-day CGM period at week 13 after randomization
measure: Daily glucose standard deviation (SD) within 12 hours (6AM-6PM) at week 13
time frame: 7 days
description: Daily SD of CGM glucose within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization
measure: Overall SD of glucose within 12 hours (6AM-6PM) at week 13
time frame: 7 days
description: Overall SD of CGM glucose within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization
measure: Mean of glucose within 12 hours (6AM-6PM) at week 13
time frame: 7 days
description: Mean of CGM glucose within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization
measure: Frequency of hypoglycemia within 12 hours (6AM-6PM) at week 13
time frame: 7 days
description: Number of hypoglycemic event which is defined as CGM glucose <4.0 mmol/L for at least 15 mins (3 consecutive CGM readings) within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization
measure: Time in hypoglycemia within 12 hours (6AM-6PM) at week 13
time frame: 7 days
description: Time with CGM glucose <4.0 mmol/L within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization
measure: Frequency of hyperglycemia within 12 hours (6AM-6PM) at week 13
time frame: 7 days
description: Number of hypoglycemic event which is defined as CGM glucose >10.0 mmol/L for at least 15 mins (3 consecutive CGM readings) within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization
measure: Time in hyperglycemia within 12 hours (6AM-6PM) at week 13
time frame: 7 days
description: Time with CGM glucose >10.0 mmol/L within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization
measure: A1C mean at week 13
time frame: Week 13
description: Average of A1C at week 13 after randomization
measure: Changes A1C
time frame: 15 weeks
description: A1C value at Visit10 at 13 weeks after randomization minus A1C value at Visit 1 at week -2 (2 weeks before randomization)
measure: Proportion of A1C <7% at week 13
time frame: Week 13
description: the number of patients who have A1C <7% divided by the total number of patients who have A1C measurement at week 13 after randomization
measure: Proportion of A1C <8% at week 13
time frame: Week 13
description: the number of patients who have A1C <8% divided by the total number of patients who have A1C measurement at week 13 after randomization
measure: Mean basal insulin dose at week 13
time frame: Week 13
description: Average of basal insulin dose from patients' diary at week 13 after randomization
measure: Change in weight
time frame: 15 weeks
description: Weight difference between week 13 after randomization and baseline at week -2 (2 weeks before randomization) = weight at Visit 10 at week 13 - weight at Visit 1 at week -2.
measure: Change in waist circumference
time frame: 15 weeks
description: Waist circumference change between week 13 after randomization and baseline at week -2 (2 week before randomization)= waist circumference at Visit 10 at week 13- waist circumference at Visit 1 at week -2
measure: Change in carbohydrate intake
time frame: 14 weeks
description: Carbohydrate intake change between week 13 after randomization and baseline at week -1 = carbohydrate intake at Visit 10 at week 13 - carbohydrate intake at Visit 2 at week -1 (1 week before randomization)
measure: Proportion of patients who have A1C ≤ 7% with no hypoglycemia and no weight gain from baseline
time frame: Week 13
description: the number of patients who have A1C ≤ 7% with no hypoglycemia and no weight gain from baseline divided by the total number of patients at Week 13 after randomization
measure: Proportion of patients who have A1C ≤ 7% with no hypoglycemia and weight gain <3% from baseline
time frame: Week 13
description: the number of patients who have A1C ≤ 7% with no hypoglycemia and weight gain <3% from baseline divided by the total number of patients at Week 13 after randomization
measure: Proportion of patients who have fasting blood glucose ≤ 5.5 mmol/L without nocturnal hypoglycemia
time frame: Week 13
description: the number of patients who have fasting blood glucose ≤ 5.5 mmol/L without nocturnal hypoglycemia divided by the total number of patients at Week 13 after randomization
measure: Change in DiabMedSat Score
time frame: 14 weeks
description: DiabMedSat Score will be generated using Diabetes Medication Satisfaction (DiabMedSat) questionnaire. It measures the levels of the subjects' satisfaction with their diabetes medication(s). The range of the score is 0 to 100. The higher the score, the greater the satisfaction. The changes in the score will measure the score difference between Visit 10 at week 13 after randomization and Visit 2 at week -1 (1 week before randomization)
measure: Change in HFS Score
time frame: 14 weeks
description: HFS Score will be measured by the Hypoglycemia Fear Survey which assesses the subject's behaviors to avoid hypoglycemia and to measure the subjects' worries about hypoglycemia and its consequences in the past 3 months. The range of the score will be 0 to 132. The higher the score, the greater the fear.
The changes will be the score difference between Visit 10 at week 13 after randomization and Visit 2 at week -1 (1 week before randomization).
measure: HCP treatment satisfaction score
time frame: Week 13
description: HCP treatment satisfaction score will be generated from Healthcare Provider treatment satisfaction questionnaire. It measures the levels of satisfaction of physicians in this study when prescribing this medication at Visit 10 at week 13 after randomization. The range is 0 to 15. The higher the score, the greater the satisfaction.
arm group label: Insulin Glargine + GLP-1 RA
arm group type: Experimental
description: Insulin Soliqua (a titratable combination of insulin Glargine + GLP-1 RA) will be administered at the subject's end-of run-in phase insulin dose (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate by one unit per day until fasting glucose level of 4-5.5 mmol/L is obtained, with or without metformin.
arm group label: Basaglar/Lantus + gliclazide MR
arm group type: Active Comparator
description: Basal insulin Basaglar/Lantus will be administered at the subject's end-of run-in phase insulin dose (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate by one unit per day until fasting glucose level of 4-5.5 mmol/L is obtained, with gliclazide MR 60 mg OD, with or without metformin.
intervention type: Drug
intervention name: Basal insulin glargine and lixisenatide
description: Soliqua (insulin glargine and lixisenatide): a titratable combination of long-acting basal insulin glargine and lixisenatide (Glucagon-like peptide-1 receptor agonist)
arm group label: Insulin Glargine + GLP-1 RA
intervention type: Drug
intervention name: Basal insulin Basaglar/Lantus + gliclazide MR
description: basal long-acting insulin Basaglar/Lantus with gliclazide MR 60 mg OD
arm group label: Basaglar/Lantus + gliclazide MR
intervention type: Drug
intervention name: Metformin
description: Patients can be administered with most tolerant dose of metformin
arm group label: Basaglar/Lantus + gliclazide MR
arm group label: Insulin Glargine + GLP-1 RA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
facility: 
country: Canada
citation: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53. Erratum In: Lancet 1999 Aug 14;354(9178):602.
PMID: 9742976
citation: Lipska KJ, Yao X, Herrin J, McCoy RG, Ross JS, Steinman MA, Inzucchi SE, Gill TM, Krumholz HM, Shah ND. Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006-2013. Diabetes Care. 2017 Apr;40(4):468-475. doi: 10.2337/dc16-0985. Epub 2016 Sep 22.
PMID: 27659408
citation: Tobias DK, Pan A, Jackson CL, O'Reilly EJ, Ding EL, Willett WC, Manson JE, Hu FB. Body-mass index and mortality among adults with incident type 2 diabetes. N Engl J Med. 2014 Jan 16;370(3):233-44. doi: 10.1056/NEJMoa1304501. Erratum In: N Engl J Med. 2014 Apr 3;370(14):1368.
PMID: 24428469
citation: Scheen AJ, Van Gaal LF. Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes. Lancet Diabetes Endocrinol. 2014 Nov;2(11):911-22. doi: 10.1016/S2213-8587(14)70004-X. Epub 2014 Feb 19.
PMID: 24731666
citation: Degn KB, Brock B, Juhl CB, Djurhuus CB, Grubert J, Kim D, Han J, Taylor K, Fineman M, Schmitz O. Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes. 2004 Sep;53(9):2397-403. doi: 10.2337/diabetes.53.9.2397.
PMID: 15331551
citation: Degn KB, Juhl CB, Sturis J, Jakobsen G, Brock B, Chandramouli V, Rungby J, Landau BR, Schmitz O. One week's treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes. 2004 May;53(5):1187-94. doi: 10.2337/diabetes.53.5.1187.
PMID: 15111485
citation: Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest. 1998 Feb 1;101(3):515-20. doi: 10.1172/JCI990.
PMID: 9449682
citation: Leiter LA, Nauck MA. Efficacy and Safety of GLP-1 Receptor Agonists Across the Spectrum of Type 2 Diabetes Mellitus. Exp Clin Endocrinol Diabetes. 2017 Jul;125(7):419-435. doi: 10.1055/s-0043-103969. Epub 2017 Jul 19. German.
PMID: 28724168
citation: Zaccardi F, Htike ZZ, Webb DR, Khunti K, Davies MJ. Benefits and Harms of Once-Weekly Glucagon-like Peptide-1 Receptor Agonist Treatments: A Systematic Review and Network Meta-analysis. Ann Intern Med. 2016 Jan 19;164(2):102-13. doi: 10.7326/M15-1432. Epub 2015 Dec 8.
PMID: 26642233
citation: Rosenstock J, Fonseca VA, Gross JL, Ratner RE, Ahren B, Chow FC, Yang F, Miller D, Johnson SL, Stewart MW, Leiter LA; Harmony 6 Study Group. Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro. Diabetes Care. 2014 Aug;37(8):2317-25. doi: 10.2337/dc14-0001. Epub 2014 Jun 4.
PMID: 24898300
citation: Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH; 4B Study Group. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2763-73. doi: 10.2337/dc14-0876. Epub 2014 Jul 10.
PMID: 25011946
citation: Writing Group for the DCCT/EDIC Research Group; Orchard TJ, Nathan DM, Zinman B, Cleary P, Brillon D, Backlund JY, Lachin JM. Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality. JAMA. 2015 Jan 6;313(1):45-53. doi: 10.1001/jama.2014.16107.
PMID: 25562265
citation: Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10.
PMID: 18784090
citation: Lind M, Svensson AM, Kosiborod M, Gudbjornsdottir S, Pivodic A, Wedel H, Dahlqvist S, Clements M, Rosengren A. Glycemic control and excess mortality in type 1 diabetes. N Engl J Med. 2014 Nov 20;371(21):1972-82. doi: 10.1056/NEJMoa1408214.
PMID: 25409370
citation: Esposito K, Giugliano D, Nappo F, Marfella R; Campanian Postprandial Hyperglycemia Study Group. Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation. 2004 Jul 13;110(2):214-9. doi: 10.1161/01.CIR.0000134501.57864.66. Epub 2004 Jun 14.
PMID: 15197140
citation: Kilpatrick ES, Rigby AS, Atkin SL. A1C variability and the risk of microvascular complications in type 1 diabetes: data from the Diabetes Control and Complications Trial. Diabetes Care. 2008 Nov;31(11):2198-202. doi: 10.2337/dc08-0864. Epub 2008 Jul 23.
PMID: 18650371
citation: Bajaj HS, Venn K, Ye C, Patrick A, Kalra S, Khandwala H, Aslam N, Twum-Barima D, Aronson R. Lowest Glucose Variability and Hypoglycemia Are Observed With the Combination of a GLP-1 Receptor Agonist and Basal Insulin (VARIATION Study). Diabetes Care. 2017 Feb;40(2):194-200. doi: 10.2337/dc16-1582. Epub 2016 Dec 2.
PMID: 27913575
citation: Chiu M, Austin PC, Manuel DG, Tu JV. Comparison of cardiovascular risk profiles among ethnic groups using population health surveys between 1996 and 2007. CMAJ. 2010 May 18;182(8):E301-10. doi: 10.1503/cmaj.091676. Epub 2010 Apr 19.
PMID: 20403888
citation: Chiu M, Maclagan LC, Tu JV, Shah BR. Temporal trends in cardiovascular disease risk factors among white, South Asian, Chinese and black groups in Ontario, Canada, 2001 to 2012: a population-based study. BMJ Open. 2015 Aug 10;5(8):e007232. doi: 10.1136/bmjopen-2014-007232.
PMID: 26260346
citation: Gujral UP, Pradeepa R, Weber MB, Narayan KM, Mohan V. Type 2 diabetes in South Asians: similarities and differences with white Caucasian and other populations. Ann N Y Acad Sci. 2013 Apr;1281(1):51-63. doi: 10.1111/j.1749-6632.2012.06838.x. Epub 2013 Jan 14.
PMID: 23317344
citation: Yale JF, Berard L, Groleau M, Javadi P, Stewart J, Harris SB. TITRATION: A Randomized Study to Assess 2 Treatment Algorithms with New Insulin Glargine 300 units/mL. Can J Diabetes. 2017 Oct;41(5):478-484. doi: 10.1016/j.jcjd.2017.06.007. Epub 2017 Aug 10.
PMID: 28803820
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Metformin
mesh term: Insulin Glargine
mesh term: Lixisenatide
mesh term: Gliclazide
sharing ipd: No