<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/NCT04451837</url>
  </required_header>
  <id_info>
    <org_study_id>DIAB1</org_study_id>
    <nct_id>NCT04451837</nct_id>
  </id_info>
  <brief_title>Semaglutide and Dapagliflozin in Diabetic Patients With Different Pathophysiology</brief_title>
  <official_title>Semaglutide and Dapagliflozin in Diabetic Patients With Different Pathophysiology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Region Skane</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Göteborg University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Region Skane</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Current anti-diabetic treatment fails to stop the progressive course of the disease. Recent&#xD;
      studies have revealed a surprisingly high variability in the diabetic phenotype. The&#xD;
      investigators propose that anti-diabetic treatment should ideally target the underlying&#xD;
      pathophysiology of each individual patient. The investigators will therefore test whether the&#xD;
      effect of two approved anti-diabetic drugs differs between individuals at different ends of&#xD;
      the pathophysiological spectrum: 1) patients with poor insulin secretion, here termed SIDD&#xD;
      and 2) patients with high insulin resistance, here termed SIRD. The study may open up a new&#xD;
      avenue for more precise treatment of diabetic patients that would be of immediate clinical&#xD;
      relevance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial is a clinical phase II study that will be randomized and open-label with fixed&#xD;
      stratification variables (SIDD and SIRD) to analyze if the response to anti-diabetic drugs&#xD;
      differs between patients with distinct pathophysiology, as captured by SIDD and SIRD. The&#xD;
      compounds used are semaglutide and dapagliflozin, which will be randomized to patients of&#xD;
      each subgroup using a parallel group design.&#xD;
&#xD;
      The clusters (SIDD and SIRD) will be used as a practical tool to distinguish individuals who&#xD;
      are at different ends of the pathophysiological spectrum.&#xD;
&#xD;
      The investigators will recruit 200 patients from the ANDIS registry with HbA1c ≥42 mmol/mol&#xD;
      on metformin monotherapy. Half of them will have SIDD and half will have SIRD&#xD;
      characteristics. The patients will be randomized (open-label) to receive semaglutide or&#xD;
      dapagliflozin for six months in addition to metformin.&#xD;
&#xD;
      The investigators will recruit participants on metformin monotherapy with stable dose for the&#xD;
      last three months. Metformin dose at inclusion (as prescribed by their regular physician) is&#xD;
      maintained throughout the study; the investigatorswill correct for metformin dose in the&#xD;
      analyses. Patients randomized to add semaglutide will receive injection training at the study&#xD;
      site and inject 0.25 mg subcutaneously once weekly during the first four weeks, followed by&#xD;
      0.5 mg weekly for the subsequent four weeks and finally 1.0 mg weekly throughout the study.&#xD;
      Those randomized to dapagliflozin will receive 10 mg orally once daily in addition to&#xD;
      metformin. The participants will attend a screening visit followed by three study visits at&#xD;
      0, 3, 6 months. At the first and last study visit they will undergo an OGTT. HbA1c will be&#xD;
      measured at all study visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 10, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">December 15, 2021</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hba1c</measure>
    <time_frame>6 months</time_frame>
    <description>The primary endpoint will be the intraindividual change of HbA1c in response to semaglutide or dapagliflozin relative to baseline in the two patient groups.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Type2 Diabetes</condition>
  <arm_group>
    <arm_group_label>semaglutide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to add semaglutide (Ozempic) will receive injection training at the study site and inject 0.25 mg subcutaneously once weekly during the first four weeks, followed by 0.5 mg weekly for the subsequent four weeks and finally 1.0 mg weekly throughout the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dapagliflozin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Those randomized to dapagliflozin will receive 10 mg orally once daily in addition to metformin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Semaglutide</intervention_name>
    <description>Ozempic s.c. once weekly for 6 months</description>
    <arm_group_label>semaglutide</arm_group_label>
    <other_name>Ozempic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <description>Forxiga 10 mg p.o. once daily for 6 months</description>
    <arm_group_label>dapagliflozin</arm_group_label>
    <other_name>Forxiga</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  • Diabetes mellitus based on prior documentation or treatment with anti-hyperglycemic&#xD;
             medication or diagnosed according to the WHO criteria (random plasma glucose &gt;11.1&#xD;
             mmol/L or fasting glucose &gt;7.0 mmol/L or HbA1C ≥6.5%) and disease characteristics&#xD;
             typical for SIDD or SIRD according to the ANDIS clustering&#xD;
&#xD;
               -  Ongoing metformin therapy with constant dose the last three months&#xD;
&#xD;
               -  Age 18 years or above&#xD;
&#xD;
               -  HbA1c ≥42 and &lt;91 mmol/mol&#xD;
&#xD;
               -  Women who are not postmenopausal and who have not undergone surgical&#xD;
                  sterilization must have no current pregnancy, which will be assessed by pregnancy&#xD;
                  test, must take precautions to avoid pregnancy throughout the study and for 4&#xD;
                  weeks after intake of the last dose and must be willing to use highly effective&#xD;
                  birth control methods. Methods that can achieve a failure rate of less than 1%&#xD;
                  per year when used consistently and correctly are considered as highly effective&#xD;
                  birth control methods.&#xD;
&#xD;
               -  Willingness to take injectable and oral medication&#xD;
&#xD;
               -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Type 1 diabetes, LADA, MODY, secondary diabetes or history of diabetic ketoacidosis&#xD;
&#xD;
               -  Anti-diabetic treatment other than metformin within 90 days prior to&#xD;
                  randomization or changed metformin dose within 90 days prior to randomization&#xD;
&#xD;
               -  Known acute cardiovascular event, e.g. transient ischemic attack, stroke, acute&#xD;
                  coronary syndrome, decompensated heart failure, coronary by-pass surgery or other&#xD;
                  coronary vessel intervention within 90 days prior to screening.&#xD;
&#xD;
               -  Heart failure NYHA class IV&#xD;
&#xD;
               -  History of acute or chronic pancreatitis&#xD;
&#xD;
               -  Known liver cirrhosis&#xD;
&#xD;
               -  Blood pressure above 170/110 mm Hg&#xD;
&#xD;
               -  A level of aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT),&#xD;
                  ALP or bilirubin of more than three times the upper limit of the normal range&#xD;
&#xD;
               -  Current chronic daily treatment with an oral steroid at a dose equivalent to oral&#xD;
                  prednisolone ≥10 mg (e.g., betamethasone ≥1.2 mg, dexamethasone ≥1.5 mg,&#xD;
                  hydrocortisone ≥40 mg)&#xD;
&#xD;
               -  Pregnancy or breast-feeding&#xD;
&#xD;
               -  Known galactose intolerance, total lactase deficiency or glucose-galactose&#xD;
                  malabsorption.&#xD;
&#xD;
               -  Estimated glomerular filtration rate &lt;45 ml/min/1,73 m2 or unstable or rapidly&#xD;
                  progressing renal disease&#xD;
&#xD;
               -  Participant unable to understand the study information herself or himself&#xD;
&#xD;
               -  Involvement in the planning and/or conduct of the study&#xD;
&#xD;
               -  Participation in other clinical trial which may affect the outcome of the present&#xD;
                  study&#xD;
&#xD;
               -  Any condition or treatment that in the judgment of the investigator makes it&#xD;
                  difficult or unsafe to participate in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anders Rosengren</last_name>
    <role>Principal Investigator</role>
    <affiliation>Region Skåne</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Anders Rosengrentest</name>
      <address>
        <city>Malmö</city>
        <state>Skane</state>
        <zip>20502</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>June 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>October 19, 2022</last_update_submitted>
  <last_update_submitted_qc>October 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dapagliflozin</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/NCT04451837
org study id: DIAB1
nct id: NCT04451837
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Current anti-diabetic treatment fails to stop the progressive course of the disease. Recent
      studies have revealed a surprisingly high variability in the diabetic phenotype. The
      investigators propose that anti-diabetic treatment should ideally target the underlying
      pathophysiology of each individual patient. The investigators will therefore test whether the
      effect of two approved anti-diabetic drugs differs between individuals at different ends of
      the pathophysiological spectrum: 1) patients with poor insulin secretion, here termed SIDD
      and 2) patients with high insulin resistance, here termed SIRD. The study may open up a new
      avenue for more precise treatment of diabetic patients that would be of immediate clinical
      relevance.
The trial is a clinical phase II study that will be randomized and open-label with fixed
      stratification variables (SIDD and SIRD) to analyze if the response to anti-diabetic drugs
      differs between patients with distinct pathophysiology, as captured by SIDD and SIRD. The
      compounds used are semaglutide and dapagliflozin, which will be randomized to patients of
      each subgroup using a parallel group design.

      The clusters (SIDD and SIRD) will be used as a practical tool to distinguish individuals who
      are at different ends of the pathophysiological spectrum.

      The investigators will recruit 200 patients from the ANDIS registry with HbA1c ≥42 mmol/mol
      on metformin monotherapy. Half of them will have SIDD and half will have SIRD
      characteristics. The patients will be randomized (open-label) to receive semaglutide or
      dapagliflozin for six months in addition to metformin.

      The investigators will recruit participants on metformin monotherapy with stable dose for the
      last three months. Metformin dose at inclusion (as prescribed by their regular physician) is
      maintained throughout the study; the investigatorswill correct for metformin dose in the
      analyses. Patients randomized to add semaglutide will receive injection training at the study
      site and inject 0.25 mg subcutaneously once weekly during the first four weeks, followed by
      0.5 mg weekly for the subsequent four weeks and finally 1.0 mg weekly throughout the study.
      Those randomized to dapagliflozin will receive 10 mg orally once daily in addition to
      metformin. The participants will attend a screening visit followed by three study visits at
      0, 3, 6 months. At the first and last study visit they will undergo an OGTT. HbA1c will be
      measured at all study visits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Hba1c
time frame: 6 months
description: The primary endpoint will be the intraindividual change of HbA1c in response to semaglutide or dapagliflozin relative to baseline in the two patient groups.
arm group label: semaglutide
arm group type: Active Comparator
description: Patients randomized to add semaglutide (Ozempic) will receive injection training at the study site and inject 0.25 mg subcutaneously once weekly during the first four weeks, followed by 0.5 mg weekly for the subsequent four weeks and finally 1.0 mg weekly throughout the study.
arm group label: dapagliflozin
arm group type: Active Comparator
description: Those randomized to dapagliflozin will receive 10 mg orally once daily in addition to metformin.
intervention type: Drug
intervention name: Semaglutide
description: Ozempic s.c. once weekly for 6 months
arm group label: semaglutide
other name: Ozempic
intervention type: Drug
intervention name: Dapagliflozin
description: Forxiga 10 mg p.o. once daily for 6 months
arm group label: dapagliflozin
other name: Forxiga
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anders Rosengren
role: Principal Investigator
affiliation: Region Skåne
facility: 
country: Sweden
responsible party type: Sponsor
mesh term: Dapagliflozin
sharing ipd: No