<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/NCT02981069</url>
  </required_header>
  <id_info>
    <org_study_id>HSC20160597H</org_study_id>
    <nct_id>NCT02981069</nct_id>
  </id_info>
  <brief_title>Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in T2DM</brief_title>
  <official_title>Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in Type 2 Diabetes Mellitus (T2DM)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center at San Antonio</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Texas Health Science Center at San Antonio</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, the researchers hope to learn about SGLT2 inhibition on EGP (endogenous&#xD;
      glucose production) and plasma glucose concentration in diabetic subjects. Researchers will&#xD;
      examine diabetes and the role of increased plasma glucagon, decline in plasma insulin, and&#xD;
      fall in plasma glucose concentration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will examine whether the coadministration of exenatide plus dapagliflozin will&#xD;
      prevent the increase in EGP and result in an additive or even synergistic decrease in plasma&#xD;
      glucose concentration compared to each agent alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 15, 2017</start_date>
  <completion_date type="Actual">March 19, 2023</completion_date>
  <primary_completion_date type="Actual">July 14, 2022</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Endogenous Glucose Production (EGP) After Acute Exposure to a Single Dose and Again After 16 Weeks of Treatment</measure>
    <time_frame>ACUTE [after a single dose of each study drug or placebo]</time_frame>
    <description>After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg + exenatide 5 ug [ACUTE STUDY].</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Endogenous Glucose Production (EGP) After 16 Weeks of Treatment With Each Study Drug.</measure>
    <time_frame>16 weeks</time_frame>
    <description>After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) exenatide 5 ug subcutaneously; (ii) dapagliflozin (10 mg); and (iii) dapagliflozin 10 mg + exenatide 5 ug. Only three groups will be followed for 16 weeks since subjects are diabetic and placebo is not appropriate to use for this period. Again, subjects will be randomized to treatment with either exenatide, dapagliflozin or both drugs in combination. Repeat EGP will be measured again at 16 weeks as described above and data will be compared to respective &quot;acute&quot; studies.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Fasting Plasma Glucose (FPG) Concentration</measure>
    <time_frame>16 weeks</time_frame>
    <description>The change in (FPG) above baseline following administration of study interventions after 16 weeks of treatment with each study drug(s) compared to data obtained during the acute exposure. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma Glucagon Concentration</measure>
    <time_frame>Baseline to 16 weeks</time_frame>
    <description>Measurement of change in plasma glucagon concentration after 16 weeks of treatment with each study drug(s) compared to acute exposure at baseline. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma Insulin Concentration</measure>
    <time_frame>Baseline to 16 weeks</time_frame>
    <description>Measurement of change in plasma insulin concentration from baseline to 16 weeks following treatment with each study drug(s). Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Byetta / Bydureon</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Exenatide:&#xD;
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dapagliflozin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Byetta/Bydureon plus Dapagliflozin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Exenatide:&#xD;
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS&#xD;
Dapagliflozin:&#xD;
4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo group (4 weeks and 12 weeks)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <description>10mg</description>
    <arm_group_label>Byetta/Bydureon plus Dapagliflozin</arm_group_label>
    <arm_group_label>Dapagliflozin</arm_group_label>
    <other_name>Farxiga</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exenatide</intervention_name>
    <description>Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)</description>
    <arm_group_label>Byetta / Bydureon</arm_group_label>
    <arm_group_label>Byetta/Bydureon plus Dapagliflozin</arm_group_label>
    <other_name>Byetta, Bydureon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo for Dapagliflozin</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. BMI = 25-35 kg/m^2&#xD;
&#xD;
          2. must be drug naïve and/or on a stable dose (more than 3 months) of metformin and/or&#xD;
             sulfonylurea&#xD;
&#xD;
          3. HbA1c &gt;7.0% and &lt;10.0%&#xD;
&#xD;
          4. Other than diabetes, subjects must be in good general health as determined by physical&#xD;
             exam, medical history, blood chemistries, CBC, TSH, T4, EKG and urinanalysis.&#xD;
&#xD;
          5. Only subjects whose body weight has been stable (± 3 lbs) over the preceding three&#xD;
             months and who do not participate in an excessively heavy exercise program will be&#xD;
             included.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of significant systemic disease, heart problems including congestive heart&#xD;
             failure, unstable angina or acute myocardial infarction, current infectious liver&#xD;
             disease, acute stroke or transient ischemic attacks, history of pancreatitis,&#xD;
             urosepsis and pyelonephritis, genital mycotic infections, or Type 1 diabetes mellitus&#xD;
&#xD;
          2. Any hepatic diseases in the past (infectious liver disease, viral hepatitis, toxic&#xD;
             hepatic damage, jaundice of unknown etiology) or severe hepatic insufficiency and/or&#xD;
             significant abnormal liver function tests defined as aspartate aminotransferase (AST)&#xD;
             &gt;3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) &gt;3x ULN&#xD;
&#xD;
          3. Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women or ≥1.5 mg/dl for&#xD;
             men, or eGFR &lt;60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal&#xD;
             disease or end stage renal disease.&#xD;
&#xD;
          4. Uncontrolled thyroid disease , Cushing's syndrome, congenital adrenal hyperplasia or&#xD;
             hyperprolactinemia&#xD;
&#xD;
          5. Significantly elevated triglyceride levels (fasting triglyceride &gt; 400 mg/dl),&#xD;
             uncontrolled increased LDL-C&#xD;
&#xD;
          6. Untreated or poorly controlled hypertension (sitting blood pressure &gt; 160/95 mm Hg)&#xD;
&#xD;
          7. Use of anti-obesity drugs or weight loss medications (prescription or OTC) and&#xD;
             medications known to exacerbate glucose tolerance (such as isotretinoin, , GnRH&#xD;
             agonists, glucocorticoids, anabolic steroids, C-19 progestins) stopped for at least 8&#xD;
             weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha&#xD;
             reductase inhibitors (finesteride, spironolactone, flutamide) stopped for at least 4&#xD;
             weeks&#xD;
&#xD;
          8. Prior history of a malignant disease requiring chemotherapy, prior history of bladder&#xD;
             cancer regardless treatment&#xD;
&#xD;
          9. Patients at risk for volume depletion due to co-existing conditions or concomitant&#xD;
             medications, such as loop diuretics should have careful monitoring of their volume&#xD;
             status&#xD;
&#xD;
         10. History of unexplained microscopic or gross hematuria, or microscopic hematuria at&#xD;
             visit 1, confirmed by a follow-up sample at next scheduled visit.&#xD;
&#xD;
         11. Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g.&#xD;
             anaphylaxis, angioedema, exfoliative skin conditions&#xD;
&#xD;
         12. Known hypersensitivity or contraindications to use GLP1 receptor agonists (exenatide,&#xD;
             liraglutide)&#xD;
&#xD;
         13. Use of , thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2&#xD;
             inhibitors stopped for at least 8 weeks.&#xD;
&#xD;
         14. Eating disorders (anorexia, bulimia) or gastrointestinal disorders&#xD;
&#xD;
         15. Suspected pregnancy (documented negative serum β-hCG test), desiring pregnancy in next&#xD;
             6 months, breastfeeding, or known pregnancy in last 2 months&#xD;
&#xD;
         16. Active history of illicit substance abuse or significant intake of alcohol&#xD;
&#xD;
         17. Having a history of bariatric surgery&#xD;
&#xD;
         18. Patient not willing to use two barrier method contraception during study period&#xD;
             (unless sterilized or have an IUD)&#xD;
&#xD;
         19. Debilitating uncontrolled psychiatric disorder such as psychosis or neurological&#xD;
             condition that might confound outcome variables&#xD;
&#xD;
         20. Inability or refusal to comply with protocol&#xD;
&#xD;
         21. Current participation or participation in an experimental drug study in previous three&#xD;
             months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eugenio Cersosimo, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Texas Health Science Center at San Antonio</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Health Science Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <results_first_submitted>March 20, 2023</results_first_submitted>
  <results_first_submitted_qc>June 28, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 20, 2023</results_first_posted>
  <last_update_submitted>June 28, 2023</last_update_submitted>
  <last_update_submitted_qc>June 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Insulin Resistance</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 8, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT02981069/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Type 2 diabetes with significant clinical complications were excluded</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Byetta / Bydureon</title>
          <description>Exenatide:&#xD;
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc&#xD;
Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)</description>
        </group>
        <group group_id="P2">
          <title>Dapagliflozin</title>
          <description>4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg&#xD;
Dapagliflozin: 10mg</description>
        </group>
        <group group_id="P3">
          <title>Byetta/Bydureon Plus Dapagliflozin</title>
          <description>Exenatide:&#xD;
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS&#xD;
Dapagliflozin:&#xD;
4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg&#xD;
Dapagliflozin: 10mg&#xD;
Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)</description>
        </group>
        <group group_id="P4">
          <title>Placebo</title>
          <description>Placebo group (4 weeks and 12 weeks)&#xD;
Placebo: Placebo for Dapagliflozin</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Acute Portion of Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="25"/>
                <participants group_id="P4" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="25"/>
                <participants group_id="P4" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>16 Week Drug Administration Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="25"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="25"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Byetta / Bydureon</title>
          <description>Exenatide:&#xD;
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc&#xD;
Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)</description>
        </group>
        <group group_id="B2">
          <title>Dapagliflozin</title>
          <description>4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg&#xD;
Dapagliflozin: 10mg</description>
        </group>
        <group group_id="B3">
          <title>Byetta/Bydureon Plus Dapagliflozin</title>
          <description>Exenatide:&#xD;
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS&#xD;
Dapagliflozin:&#xD;
4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg&#xD;
Dapagliflozin: 10mg&#xD;
Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)</description>
        </group>
        <group group_id="B4">
          <title>Placebo</title>
          <description>Placebo group (4 weeks and 12 weeks)&#xD;
Placebo: Placebo for Dapagliflozin</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
            <count group_id="B2" value="25"/>
            <count group_id="B3" value="25"/>
            <count group_id="B4" value="15"/>
            <count group_id="B5" value="90"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="87"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52" spread="3"/>
                    <measurement group_id="B2" value="51" spread="2"/>
                    <measurement group_id="B3" value="49" spread="4"/>
                    <measurement group_id="B4" value="54" spread="3"/>
                    <measurement group_id="B5" value="52" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="67"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="61"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Endogenous Glucose Production (EGP) After Acute Exposure to a Single Dose and Again After 16 Weeks of Treatment</title>
        <description>After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg + exenatide 5 ug [ACUTE STUDY].</description>
        <time_frame>ACUTE [after a single dose of each study drug or placebo]</time_frame>
        <population>Type 2 diabetes</population>
        <group_list>
          <group group_id="O1">
            <title>EXENATIDE</title>
            <description>Exenatide:&#xD;
After acute exposure to a single dose of Exenatide, 5 mcg.</description>
          </group>
          <group group_id="O2">
            <title>Dapagliflozin</title>
            <description>After acute single dose exposure of Dapagliflozin, Farxiga, 10mg</description>
          </group>
          <group group_id="O3">
            <title>Exenatide Plus Dapagliflozin</title>
            <description>After acute exposure to both dapagliflozin, farxiga 10 mg orally and a single subcutaneous injection of Exenatide</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>After a single dose of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Endogenous Glucose Production (EGP) After Acute Exposure to a Single Dose and Again After 16 Weeks of Treatment</title>
          <description>After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg + exenatide 5 ug [ACUTE STUDY].</description>
          <population>Type 2 diabetes</population>
          <units>mg/kg.min</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="25"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.18" spread="0.02"/>
                    <measurement group_id="O2" value="0.14" spread="0.03"/>
                    <measurement group_id="O3" value="-0.08" spread="0.03"/>
                    <measurement group_id="O4" value="-0.03" spread="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Fasting Plasma Glucose (FPG) Concentration</title>
        <description>The change in (FPG) above baseline following administration of study interventions after 16 weeks of treatment with each study drug(s) compared to data obtained during the acute exposure. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.</description>
        <time_frame>16 weeks</time_frame>
        <population>type 2 diabetes</population>
        <group_list>
          <group group_id="O1">
            <title>Byetta / Bydureon</title>
            <description>Exenatide:&#xD;
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc&#xD;
Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)</description>
          </group>
          <group group_id="O2">
            <title>Dapagliflozin</title>
            <description>4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg&#xD;
Dapagliflozin: 10mg</description>
          </group>
          <group group_id="O3">
            <title>Byetta/Bydureon Plus Dapagliflozin</title>
            <description>Exenatide:&#xD;
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS&#xD;
Dapagliflozin:&#xD;
4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg&#xD;
Dapagliflozin: 10mg&#xD;
Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Fasting Plasma Glucose (FPG) Concentration</title>
          <description>The change in (FPG) above baseline following administration of study interventions after 16 weeks of treatment with each study drug(s) compared to data obtained during the acute exposure. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.</description>
          <population>type 2 diabetes</population>
          <units>mg/dl</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42" spread="1"/>
                    <measurement group_id="O2" value="72" spread="3"/>
                    <measurement group_id="O3" value="11" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Plasma Glucagon Concentration</title>
        <description>Measurement of change in plasma glucagon concentration after 16 weeks of treatment with each study drug(s) compared to acute exposure at baseline. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.</description>
        <time_frame>Baseline to 16 weeks</time_frame>
        <population>type 2 diabetes</population>
        <group_list>
          <group group_id="O1">
            <title>Dapa+Exe</title>
            <description>Combination dapagliflozin plus exenatide therapy</description>
          </group>
          <group group_id="O2">
            <title>Dapa</title>
            <description>Dapagliflozin therapy for 16 weeks</description>
          </group>
          <group group_id="O3">
            <title>Exenatide</title>
            <description>Exenatide therapy for 16 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Plasma Glucagon Concentration</title>
          <description>Measurement of change in plasma glucagon concentration after 16 weeks of treatment with each study drug(s) compared to acute exposure at baseline. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.</description>
          <population>type 2 diabetes</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" spread="2"/>
                    <measurement group_id="O2" value="5" spread="2"/>
                    <measurement group_id="O3" value="-6" spread="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Plasma Insulin Concentration</title>
        <description>Measurement of change in plasma insulin concentration from baseline to 16 weeks following treatment with each study drug(s). Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.</description>
        <time_frame>Baseline to 16 weeks</time_frame>
        <population>Type 2 diabetes</population>
        <group_list>
          <group group_id="O1">
            <title>Dapa+Exe</title>
            <description>Therapy for 16 weeks with combination exenatide plus dapagliflozin</description>
          </group>
          <group group_id="O2">
            <title>Dapa</title>
            <description>Dapagliflozin therapy for 16 weeks</description>
          </group>
          <group group_id="O3">
            <title>Exenatide</title>
            <description>Exenatide therapy for 16 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Plasma Insulin Concentration</title>
          <description>Measurement of change in plasma insulin concentration from baseline to 16 weeks following treatment with each study drug(s). Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.</description>
          <population>Type 2 diabetes</population>
          <units>microUnits/ml</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2" spread="1"/>
                    <measurement group_id="O2" value="-2" spread="2"/>
                    <measurement group_id="O3" value="3" spread="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Endogenous Glucose Production (EGP) After 16 Weeks of Treatment With Each Study Drug.</title>
        <description>After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) exenatide 5 ug subcutaneously; (ii) dapagliflozin (10 mg); and (iii) dapagliflozin 10 mg + exenatide 5 ug. Only three groups will be followed for 16 weeks since subjects are diabetic and placebo is not appropriate to use for this period. Again, subjects will be randomized to treatment with either exenatide, dapagliflozin or both drugs in combination. Repeat EGP will be measured again at 16 weeks as described above and data will be compared to respective &quot;acute&quot; studies.</description>
        <time_frame>16 weeks</time_frame>
        <population>Type 2 diabetes</population>
        <group_list>
          <group group_id="O1">
            <title>EXENATIDE</title>
            <description>Exenatide:&#xD;
After 16 weeks of treatment with Exenatide, starting with 5 mcg twice daily and at 4 weeks changed to 2 mg once weekly subcutaneously.</description>
          </group>
          <group group_id="O2">
            <title>Dapagliflozin</title>
            <description>After 16 weeks of treatment with Dapagliflozin, Farxiga, 10mg</description>
          </group>
          <group group_id="O3">
            <title>Exenatide Plus Dapagliflozin</title>
            <description>After 16 weeks of therapy with both drugs in combination.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Endogenous Glucose Production (EGP) After 16 Weeks of Treatment With Each Study Drug.</title>
          <description>After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) exenatide 5 ug subcutaneously; (ii) dapagliflozin (10 mg); and (iii) dapagliflozin 10 mg + exenatide 5 ug. Only three groups will be followed for 16 weeks since subjects are diabetic and placebo is not appropriate to use for this period. Again, subjects will be randomized to treatment with either exenatide, dapagliflozin or both drugs in combination. Repeat EGP will be measured again at 16 weeks as described above and data will be compared to respective &quot;acute&quot; studies.</description>
          <population>Type 2 diabetes</population>
          <units>mg/kg.min</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.23" spread="0.02"/>
                    <measurement group_id="O2" value="0.20" spread="0.03"/>
                    <measurement group_id="O3" value="-0.12" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline to 6 months</time_frame>
      <desc>Patient reporting and physical exam by principal investigator/nurse coordinator</desc>
      <group_list>
        <group group_id="E1">
          <title>Byetta / Bydureon</title>
          <description>Exenatide:&#xD;
4 weeks of exenatide 5 mcg twice daily followed by Bydureon 2mg sc weekly&#xD;
Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)</description>
        </group>
        <group group_id="E2">
          <title>Dapagliflozin</title>
          <description>16 weeks Dapagliflozin, Farxiga, 10mg&#xD;
Dapagliflozin: 10mg</description>
        </group>
        <group group_id="E3">
          <title>Byetta/Bydureon Plus Dapagliflozin</title>
          <description>Exenatide:&#xD;
4 weeks of exenatide followed by 12 weeks of Bydureon 2mg sc once weekly PLUS&#xD;
Dapagliflozin:&#xD;
16 weeks Dapagliflozin, Farxiga, 10mg&#xD;
Dapagliflozin: 10mg&#xD;
Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>16 weeks of placebo administration</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="25"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea and Vomiting</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Genital Mycosis</sub_title>
                <description>Nausea and Vomiting</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Professor</name_or_title>
      <organization>University of Texas Health San Antonio</organization>
      <phone>12103587200</phone>
      <email>cersosimo@uthscsa.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02981069
org study id: HSC20160597H
nct id: NCT02981069
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
In this study, the researchers hope to learn about SGLT2 inhibition on EGP (endogenous
      glucose production) and plasma glucose concentration in diabetic subjects. Researchers will
      examine diabetes and the role of increased plasma glucagon, decline in plasma insulin, and
      fall in plasma glucose concentration.
This study will examine whether the coadministration of exenatide plus dapagliflozin will
      prevent the increase in EGP and result in an additive or even synergistic decrease in plasma
      glucose concentration compared to each agent alone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Endogenous Glucose Production (EGP) After Acute Exposure to a Single Dose and Again After 16 Weeks of Treatment
time frame: ACUTE [after a single dose of each study drug or placebo]
description: After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg + exenatide 5 ug [ACUTE STUDY].
measure: Change in Endogenous Glucose Production (EGP) After 16 Weeks of Treatment With Each Study Drug.
time frame: 16 weeks
description: After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) exenatide 5 ug subcutaneously; (ii) dapagliflozin (10 mg); and (iii) dapagliflozin 10 mg + exenatide 5 ug. Only three groups will be followed for 16 weeks since subjects are diabetic and placebo is not appropriate to use for this period. Again, subjects will be randomized to treatment with either exenatide, dapagliflozin or both drugs in combination. Repeat EGP will be measured again at 16 weeks as described above and data will be compared to respective "acute" studies.
measure: Change in Fasting Plasma Glucose (FPG) Concentration
time frame: 16 weeks
description: The change in (FPG) above baseline following administration of study interventions after 16 weeks of treatment with each study drug(s) compared to data obtained during the acute exposure. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.
measure: Change in Plasma Glucagon Concentration
time frame: Baseline to 16 weeks
description: Measurement of change in plasma glucagon concentration after 16 weeks of treatment with each study drug(s) compared to acute exposure at baseline. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.
measure: Change in Plasma Insulin Concentration
time frame: Baseline to 16 weeks
description: Measurement of change in plasma insulin concentration from baseline to 16 weeks following treatment with each study drug(s). Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.
arm group label: Byetta / Bydureon
arm group type: Active Comparator
description: Exenatide:
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc
arm group label: Dapagliflozin
arm group type: Active Comparator
description: 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg
arm group label: Byetta/Bydureon plus Dapagliflozin
arm group type: Active Comparator
description: Exenatide:
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS
Dapagliflozin:
4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo group (4 weeks and 12 weeks)
intervention type: Drug
intervention name: Dapagliflozin
description: 10mg
arm group label: Byetta/Bydureon plus Dapagliflozin
arm group label: Dapagliflozin
other name: Farxiga
intervention type: Drug
intervention name: Exenatide
description: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)
arm group label: Byetta / Bydureon
arm group label: Byetta/Bydureon plus Dapagliflozin
other name: Byetta, Bydureon
intervention type: Drug
intervention name: Placebo
description: Placebo for Dapagliflozin
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Eugenio Cersosimo, MD,PhD
role: Principal Investigator
affiliation: The University of Texas Health Science Center at San Antonio
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin Resistance
mesh term: Dapagliflozin
mesh term: Exenatide
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 