<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/NCT03007329</url>
  </required_header>
  <id_info>
    <org_study_id>ESR-15-10882</org_study_id>
    <nct_id>NCT03007329</nct_id>
  </id_info>
  <brief_title>Effects of Combined Dapagliflozin and Exenatide Versus Dapagliflozin and Placebo on Ectopic Lipids in Patients With Uncontrolled Type 2 Diabetes Mellitus.</brief_title>
  <acronym>EXENDA</acronym>
  <official_title>A 24 Week Monocentric Prospective Randomized, Placebo-controlled Trial to Evaluate Efficacy of Combination of Exenatide and Dapagliflozin Compared to Dapagliflozin and Placebo and Its Effects on Hepatic, Myocardial and Pancreatic Fat Distribution in Patients With Uncontrolled Type 2 Diabetes Mellitus.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of Vienna</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>
      SGLT2 antagonists and GLP1 agonists are used since a relatively short period as second line&#xD;
      therapy if indicated and are well tolerated by patients featuring low risk of hypoglycaemia&#xD;
      in comparison to insulin or other oral glucose lowering drug. This new treatment options&#xD;
      offer an effective modality to lower blood glucose, if first line therapeutics fail.&#xD;
      According to national and international guidelines combination of oral glucose lowering drugs&#xD;
      is possible in multiple ways, but is currently not recommended for GLP1 agonists and SGLT2&#xD;
      inhibitors yet, as evidence and supporting studies are missing proving efficacy and safety].&#xD;
      Thus studies under standardized conditions are urgently needed to answer these unsolved&#xD;
      questions.&#xD;
&#xD;
      First results of a combination of a SGLT2 Inhibitor and a GLP1 agonist demonstrated huge&#xD;
      potential regarding glucose and weight reduction and safety issues. However, further studies&#xD;
      are necessary to elucidate potential mechanisms of combination therapy with SGLT2 inhibitors&#xD;
      and GLP1 agonists and its effect on weight loss, glucose control, effects on incretins and&#xD;
      adipokines, as well as further effects on ectopic lipid accumulation in liver and other&#xD;
      tissues as myocard or pancreas in humans.&#xD;
&#xD;
      As both monotherapies have effects on weight and metabolism, changes in abdominal,&#xD;
      subcutaneous, hepatic, myocardial or pancreatic lipid content might be speculated and are&#xD;
      focus of interest in this study. Recently GLP1 agonists were shown to have effects on hepatic&#xD;
      lipid reduction in humans with diabetes.&#xD;
&#xD;
      Hepatic lipid content and steatosis hepatis are widely discussed to have major effects on&#xD;
      progression of diabetes and cardiovascular disease. Thus reduction of lipid accumulation in&#xD;
      hepatic tissue might have an effect on diabetes progression.&#xD;
&#xD;
      Also higher myocardial lipid accumulation is seen in diabetic patients probably partly&#xD;
      responsible for higher cardiovascular risk in diabetics. So far results combining these two&#xD;
      drug classes show less weight loss as might have been expected using monotherapy, so that&#xD;
      further investigation will definitely shed light on combination of therapeutic concepts.&#xD;
&#xD;
      Facing a multiple of positive side effects (weight loss, blood pressure lowering, potential&#xD;
      protective cardiac effects) using a combination of SGLT2 and GLP1 seems to be a promising&#xD;
      therapeutic option in diabetic subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 8, 2017</start_date>
  <completion_date type="Actual">January 16, 2020</completion_date>
  <primary_completion_date type="Actual">November 26, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change in hepatic lipid content measured with magnetic resonance spectroscopy in %</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>to investigate the effects on hepatic lipid content reduction of combination therapy with dapagliflozin (10mg daily) and exenatide (2mg weekly) compared to dapagliflozin (10mg daily) and placebo given for 24 weeks in patients with type 2 diabetes mellitus and insufficient glycaemic control despite oral therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>change in myocardial lipid content measured with magnetic resonance spectroscopy in %</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>to investigate the effects on myocardial lipid content reduction of combination therapy with dapagliflozin (10mg daily) and exenatide (2mg weekly) compared to dapagliflozin (10mg daily) and placebo given for 24 weeks in patients with type 2 diabetes mellitus and insufficient glycaemic control despite oral therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in pancreatic lipid content measured with magnetic resonance spectroscopy in %</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>to investigate the effects on pancreatic lipid content reduction of combination therapy with dapagliflozin (10mg daily) and exenatide (2mg weekly) compared to dapagliflozin (10mg daily) and placebo given for 24 weeks in patients with type 2 diabetes mellitus and insufficient glycaemic control despite oral therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>baseline- week 24</time_frame>
    <description>safety and tolerability from baseline to end by number of participants with treatment related AEs and SAEs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life questionnaire</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>change from baseline in quality of live assessed by WHO Well Being Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in insulin resistance</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>change from baseline in insulin resistance assessed by HOMA IR Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in insulin sensitivity</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>change from baseline in insulin sensitivity assessed by OGIS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>energy expenditure</measure>
    <time_frame>baseline -week 24</time_frame>
    <description>change from baseline of energy expenditure assessed by indirect calorimetry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>energy intake</measure>
    <time_frame>baseline -week 24</time_frame>
    <description>change from baseline of energy intake assessed by 3 day eating protocols</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>blood pressure</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>To assess the effect of combination therapy with dapagliflozin and exenatide on blood pressure compared to dapagliflozin and placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>weight loss</measure>
    <time_frame>baseline - week 24.</time_frame>
    <description>To assess the effect of combination therapy with dapagliflozin and exenatide on weight loss compared to dapagliflozin and placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in glomerular filtration rate</measure>
    <time_frame>baseline -week 24</time_frame>
    <description>change in GFR from baseline</description>
  </secondary_outcome>
  <other_outcome>
    <measure>weight</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>change in weight from baseline</description>
  </other_outcome>
  <other_outcome>
    <measure>hip circumference</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>change in hip circumference from baseline</description>
  </other_outcome>
  <other_outcome>
    <measure>waist circumference</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>change in waist circumference from baseline</description>
  </other_outcome>
  <other_outcome>
    <measure>fasting glucose</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>change in fasting plasma glucose from baseline</description>
  </other_outcome>
  <other_outcome>
    <measure>HbA1c reduction &gt;= 0.5%</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>% of patient with HbA1c reduction of more than 0.5%</description>
  </other_outcome>
  <other_outcome>
    <measure>weight reduction &gt;= 5%</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>% of patient with weight reduction of more than 5%</description>
  </other_outcome>
  <other_outcome>
    <measure>change in triglycerides</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>change in triglycerides from baseline</description>
  </other_outcome>
  <other_outcome>
    <measure>change in cholesterol</measure>
    <time_frame>baseline - week 24</time_frame>
    <description>change in cholesterol from baseline</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Steatosis, Liver</condition>
  <condition>Type2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Dapagliflozin &amp; Exenatide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dapagliflozin 10mg orally once daily &amp; Exenatide 2mg subcutaneous once weekly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dapagliflozin &amp; Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Dapagliflozin 10mg orally once daily &amp; Exenatide matching Placebo 2mg subcutaneous once weekly</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exenatide</intervention_name>
    <description>Exenatide will be combined with Dapagliflozin</description>
    <arm_group_label>Dapagliflozin &amp; Exenatide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exenatide matching Placebo</intervention_name>
    <description>Exenatide matching Placebo will be combined with Dapagliflozin</description>
    <arm_group_label>Dapagliflozin &amp; Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <description>Dapagliflozin, in both arms</description>
    <arm_group_label>Dapagliflozin &amp; Exenatide</arm_group_label>
    <arm_group_label>Dapagliflozin &amp; Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        T2DM&#xD;
&#xD;
          -  Sex: male and female&#xD;
&#xD;
          -  HbA1c &gt;=6.5 and &lt;=11&#xD;
&#xD;
          -  Age &gt;=18 and &lt;=75 years&#xD;
&#xD;
          -  BMI&gt;=25kg/m2&#xD;
&#xD;
          -  Metformin&gt;=1000mg daily, 8 weeks stable dose Please note: Type 2 diabetes mellitus&#xD;
             patients treated with less than 1000 mg metformin per day can only be included if the&#xD;
             investigator considers the patient to be on the maximum tolerated dose and the&#xD;
             investigator has documented the reason why uptitration to 1000 mg was not possible&#xD;
&#xD;
          -  able and willing to not change diet and physical activity during enrollment in study&#xD;
&#xD;
          -  consent and able to give informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  other diabetes diagnosis than T2DM&#xD;
&#xD;
          -  patients on other antidiabetic medication (Sulfonylurea, Glitazone, insulin for more&#xD;
             than 2 weeks (see below), SGLT2 inhibitors, GLP1 agonist, nateglinide, repaglinide,&#xD;
             acarbose, DPP4 inhibitors)&#xD;
&#xD;
          -  Subjects currently or previously treated with insulin (with the exception of emergency&#xD;
             situations in which insulin was given for less than 14 consecutive days, but not&#xD;
             within the last 3 months before screening)&#xD;
&#xD;
          -  known intolerance against study medication&#xD;
&#xD;
          -  Contraindications including hypersensitivity known to metformin according to the local&#xD;
             label&#xD;
&#xD;
          -  recurrent urinary tract infections&#xD;
&#xD;
          -  GFR &lt; 60&#xD;
&#xD;
          -  Liver enzymes above 3 fold normal range&#xD;
&#xD;
          -  Bilirubin higher 3 fold normal range&#xD;
&#xD;
          -  Any other clinical condition that would jeopardize patients safety while participating&#xD;
             in this clinical trial&#xD;
&#xD;
          -  disease at screening (other than NAFLD) such as relevant cardiovascular,&#xD;
             gastrointestinal, hepatic, neurologic, psychiatric, endocrine (i.e. pancreatic) except&#xD;
             T2DM, hematologic, malignant, infection or other major systemic diseases making&#xD;
             implementation of the protocol or interpretation of the study results difficult&#xD;
&#xD;
          -  history of pancreatitis&#xD;
&#xD;
          -  Known autoimmune disease or chronic inflammatory condition&#xD;
&#xD;
          -  Myocardial infarction or stroke within 6 months prior to screening&#xD;
&#xD;
          -  Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell&#xD;
             (e.g.malaria, babesiosis, haemolytic anaemia)&#xD;
&#xD;
          -  Other liver disease including chronic viral hepatitis (B or C), alcohol abuse,&#xD;
             hemochromatosis, alpha-1antitrypsin deficiency, autoimmune hepatitis, Wilson's&#xD;
             disease, primary sclerosing cholangitis or primary biliary cirrhosis, or liver&#xD;
             cirrhosis of any etiology&#xD;
&#xD;
          -  malignancy within the last 5 years before randomisation&#xD;
&#xD;
          -  medullary thyroid cancer&#xD;
&#xD;
          -  family history of multiple endocrine neoplasia syndrome&#xD;
&#xD;
          -  Alcohol or drug abuse within the 3 months prior to informed consent that would&#xD;
             interfere with trial participation or any ongoing condition leading to a decreased&#xD;
             compliance to study procedures or study drug intake&#xD;
&#xD;
          -  Presence of any absolute or relative contraindication for the conduct of an MRI&#xD;
             investigation, such as cardiac pacemakers, ferromagnetic haemostatic clips in the&#xD;
             central nervous system, metallic splinters in the eye, ferromagnetic or electronically&#xD;
             operated active devices like automatic cardioverter defibrillators,cochlear implants,&#xD;
             insulin pumps and nerve stimulators, prosthetic heart valves etc.&#xD;
&#xD;
          -  History of bariatric surgery&#xD;
&#xD;
          -  Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to&#xD;
             informed consent or any other treatment at the time of screening (i.e. surgery,&#xD;
             aggressive diet regimen, etc.) leading to unstable body weight&#xD;
&#xD;
          -  Subjects receiving antihypertensive medication and/or thyroid hormones, the dose(s) of&#xD;
             which have not been stable for at least 6 weeks prior to baseline&#xD;
&#xD;
          -  Current treatment with systemic steroids at time of informed consent (Treatment with&#xD;
             local and inhaled steroids is allowed)&#xD;
&#xD;
          -  Use of drugs potentially associated with NAFLD for more than 2 consecutive weeks in&#xD;
             the 6 months prior to screening.&#xD;
&#xD;
          -  Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk&#xD;
             thistle, anti-TNF therapies,) in the 3 months prior to randomization.&#xD;
&#xD;
          -  Donation of blood (&gt; 400 mL) during the previous 3 months prior to the screening visit&#xD;
             or during the duration of the study&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within 30 days prior to&#xD;
             informed consent.&#xD;
&#xD;
          -  Any subject who is the investigator or any coinvestigator, research assistant,&#xD;
             pharmacist, study coordinator, other staff thereof, directly involved in the conduct&#xD;
             of the protocol.&#xD;
&#xD;
          -  Pre-menopausal women (last menstruation ≤1 year prior to informed consent) who:&#xD;
&#xD;
          -  are nursing or pregnant or&#xD;
&#xD;
          -  are of child-bearing potential and are not practising an acceptable method of birth&#xD;
             control, or do not plan to continue using this method throughout the study and do not&#xD;
             agree to submit to periodic pregnancy testing during participation in the trial.&#xD;
             Acceptable methods of birth control include tubal ligation, transdermal patch, intra&#xD;
             uterine devices/systems (IUDs/IUSs), oral, implantable or injectable&#xD;
             contraceptives,sexual abstinence,( if acceptable by local authorities) double barrier&#xD;
             method and vasectomised partner.&#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>Alexandra Kautzky-Willer, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dep. of Medicine III, Div. of Endocrinology, Gender Medicine Unit</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Abt. für Endokrinologie &amp; Stoffwechsel, Univ. Klin f. Innere Medizin III</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <results_reference>
    <citation>Harreiter J, Just I, Leutner M, Bastian M, Brath H, Schelkshorn C, Klepochova R, Krssak M, Kautzky-Willer A. Combined exenatide and dapagliflozin has no additive effects on reduction of hepatocellular lipids despite better glycaemic control in patients with type 2 diabetes mellitus treated with metformin: EXENDA, a 24-week, prospective, randomized, placebo-controlled pilot trial. Diabetes Obes Metab. 2021 May;23(5):1129-1139. doi: 10.1111/dom.14319. Epub 2021 Feb 10.</citation>
    <PMID>33464703</PMID>
  </results_reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>April 8, 2022</last_update_submitted>
  <last_update_submitted_qc>April 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Alexandra Kautzky-Willer</investigator_full_name>
    <investigator_title>Prof. Dr.</investigator_title>
  </responsible_party>
  <keyword>SGLT2 inhibitor</keyword>
  <keyword>GLP1 agonist</keyword>
  <keyword>type 2 Diabetes</keyword>
  <keyword>steatosis of the liver</keyword>
  <keyword>ectopic lipids</keyword>
  <keyword>combined therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fatty Liver</mesh_term>
    <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>Dapagliflozin</mesh_term>
    <mesh_term>Exenatide</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03007329
org study id: ESR-15-10882
nct id: NCT03007329
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
SGLT2 antagonists and GLP1 agonists are used since a relatively short period as second line
      therapy if indicated and are well tolerated by patients featuring low risk of hypoglycaemia
      in comparison to insulin or other oral glucose lowering drug. This new treatment options
      offer an effective modality to lower blood glucose, if first line therapeutics fail.
      According to national and international guidelines combination of oral glucose lowering drugs
      is possible in multiple ways, but is currently not recommended for GLP1 agonists and SGLT2
      inhibitors yet, as evidence and supporting studies are missing proving efficacy and safety].
      Thus studies under standardized conditions are urgently needed to answer these unsolved
      questions.

      First results of a combination of a SGLT2 Inhibitor and a GLP1 agonist demonstrated huge
      potential regarding glucose and weight reduction and safety issues. However, further studies
      are necessary to elucidate potential mechanisms of combination therapy with SGLT2 inhibitors
      and GLP1 agonists and its effect on weight loss, glucose control, effects on incretins and
      adipokines, as well as further effects on ectopic lipid accumulation in liver and other
      tissues as myocard or pancreas in humans.

      As both monotherapies have effects on weight and metabolism, changes in abdominal,
      subcutaneous, hepatic, myocardial or pancreatic lipid content might be speculated and are
      focus of interest in this study. Recently GLP1 agonists were shown to have effects on hepatic
      lipid reduction in humans with diabetes.

      Hepatic lipid content and steatosis hepatis are widely discussed to have major effects on
      progression of diabetes and cardiovascular disease. Thus reduction of lipid accumulation in
      hepatic tissue might have an effect on diabetes progression.

      Also higher myocardial lipid accumulation is seen in diabetic patients probably partly
      responsible for higher cardiovascular risk in diabetics. So far results combining these two
      drug classes show less weight loss as might have been expected using monotherapy, so that
      further investigation will definitely shed light on combination of therapeutic concepts.

      Facing a multiple of positive side effects (weight loss, blood pressure lowering, potential
      protective cardiac effects) using a combination of SGLT2 and GLP1 seems to be a promising
      therapeutic option in diabetic subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: change in hepatic lipid content measured with magnetic resonance spectroscopy in %
time frame: baseline - week 24
description: to investigate the effects on hepatic lipid content reduction of combination therapy with dapagliflozin (10mg daily) and exenatide (2mg weekly) compared to dapagliflozin (10mg daily) and placebo given for 24 weeks in patients with type 2 diabetes mellitus and insufficient glycaemic control despite oral therapy.
measure: change in myocardial lipid content measured with magnetic resonance spectroscopy in %
time frame: baseline - week 24
description: to investigate the effects on myocardial lipid content reduction of combination therapy with dapagliflozin (10mg daily) and exenatide (2mg weekly) compared to dapagliflozin (10mg daily) and placebo given for 24 weeks in patients with type 2 diabetes mellitus and insufficient glycaemic control despite oral therapy.
measure: change in pancreatic lipid content measured with magnetic resonance spectroscopy in %
time frame: baseline - week 24
description: to investigate the effects on pancreatic lipid content reduction of combination therapy with dapagliflozin (10mg daily) and exenatide (2mg weekly) compared to dapagliflozin (10mg daily) and placebo given for 24 weeks in patients with type 2 diabetes mellitus and insufficient glycaemic control despite oral therapy.
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: baseline- week 24
description: safety and tolerability from baseline to end by number of participants with treatment related AEs and SAEs
measure: Quality of Life questionnaire
time frame: baseline - week 24
description: change from baseline in quality of live assessed by WHO Well Being Index
measure: change in insulin resistance
time frame: baseline - week 24
description: change from baseline in insulin resistance assessed by HOMA IR Index
measure: change in insulin sensitivity
time frame: baseline - week 24
description: change from baseline in insulin sensitivity assessed by OGIS
measure: energy expenditure
time frame: baseline -week 24
description: change from baseline of energy expenditure assessed by indirect calorimetry
measure: energy intake
time frame: baseline -week 24
description: change from baseline of energy intake assessed by 3 day eating protocols
measure: blood pressure
time frame: baseline - week 24
description: To assess the effect of combination therapy with dapagliflozin and exenatide on blood pressure compared to dapagliflozin and placebo.
measure: weight loss
time frame: baseline - week 24.
description: To assess the effect of combination therapy with dapagliflozin and exenatide on weight loss compared to dapagliflozin and placebo.
measure: change in glomerular filtration rate
time frame: baseline -week 24
description: change in GFR from baseline
measure: weight
time frame: baseline - week 24
description: change in weight from baseline
measure: hip circumference
time frame: baseline - week 24
description: change in hip circumference from baseline
measure: waist circumference
time frame: baseline - week 24
description: change in waist circumference from baseline
measure: fasting glucose
time frame: baseline - week 24
description: change in fasting plasma glucose from baseline
measure: HbA1c reduction >= 0.5%
time frame: baseline - week 24
description: % of patient with HbA1c reduction of more than 0.5%
measure: weight reduction >= 5%
time frame: baseline - week 24
description: % of patient with weight reduction of more than 5%
measure: change in triglycerides
time frame: baseline - week 24
description: change in triglycerides from baseline
measure: change in cholesterol
time frame: baseline - week 24
description: change in cholesterol from baseline
arm group label: Dapagliflozin & Exenatide
arm group type: Active Comparator
description: Dapagliflozin 10mg orally once daily & Exenatide 2mg subcutaneous once weekly
arm group label: Dapagliflozin & Placebo
arm group type: Placebo Comparator
description: Dapagliflozin 10mg orally once daily & Exenatide matching Placebo 2mg subcutaneous once weekly
intervention type: Drug
intervention name: Exenatide
description: Exenatide will be combined with Dapagliflozin
arm group label: Dapagliflozin & Exenatide
intervention type: Drug
intervention name: Exenatide matching Placebo
description: Exenatide matching Placebo will be combined with Dapagliflozin
arm group label: Dapagliflozin & Placebo
intervention type: Drug
intervention name: Dapagliflozin
description: Dapagliflozin, in both arms
arm group label: Dapagliflozin & Exenatide
arm group label: Dapagliflozin & Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Alexandra Kautzky-Willer, Prof. Dr.
role: Principal Investigator
affiliation: Dep. of Medicine III, Div. of Endocrinology, Gender Medicine Unit
facility: 
country: Austria
citation: Harreiter J, Just I, Leutner M, Bastian M, Brath H, Schelkshorn C, Klepochova R, Krssak M, Kautzky-Willer A. Combined exenatide and dapagliflozin has no additive effects on reduction of hepatocellular lipids despite better glycaemic control in patients with type 2 diabetes mellitus treated with metformin: EXENDA, a 24-week, prospective, randomized, placebo-controlled pilot trial. Diabetes Obes Metab. 2021 May;23(5):1129-1139. doi: 10.1111/dom.14319. Epub 2021 Feb 10.
PMID: 33464703
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Alexandra Kautzky-Willer
investigator title: Prof. Dr.
mesh term: Fatty Liver
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Dapagliflozin
mesh term: Exenatide