<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/NCT02969798</url>
  </required_header>
  <id_info>
    <org_study_id>HSC20130414H</org_study_id>
    <secondary_id>R01DK024092-34</secondary_id>
    <nct_id>NCT02969798</nct_id>
  </id_info>
  <brief_title>Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)</brief_title>
  <official_title>Preservation of Beta Cell Function in Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)</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>American Diabetes Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Texas Health Science Center at San Antonio</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      HYPOTHESIS: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have distinct&#xD;
      pathophysiologic etiologies. Therefore, therapeutic interventions designed to correct the&#xD;
      specific underlying pathogenic abnormalities in IGT and IFG will be required to optimally&#xD;
      prevent the progressive beta cell failure and development of overt type 2 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      SPECIFIC AIMS:&#xD;
&#xD;
        1. To examine the effect of the following pharmacologic interventions on beta cell&#xD;
           function, insulin sensitivity, and glucose tolerance status in individuals with isolated&#xD;
           impaired glucose tolerance (IGT): (i) treatment with the renal Sodium-glucose&#xD;
           co-transporter 2 (SGLT2) inhibitor inhibitor, dapagliflozin; (ii) treatment with the&#xD;
           inhibitors of dipeptidyl peptidase 4, also DPP4, saxagliptin ; (iii) treatment with the&#xD;
           thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin.&#xD;
&#xD;
        2. To examine the effect of the following pharmacologic interventions on beta cell&#xD;
           function, insulin sensitivity, and glucose tolerance status in individuals with isolated&#xD;
           impaired fasting glucose (IFG): (i) treatment with the renal SGLT2 inhibitor,&#xD;
           dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with&#xD;
           the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin.&#xD;
&#xD;
        3. To examine the effect of the following pharmacologic interventions on beta cell&#xD;
           function, insulin sensitivity, and glucose tolerance status in individuals with combined&#xD;
           impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG): i) treatment with&#xD;
           the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor,&#xD;
           saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment&#xD;
           with the biguanide, metformin.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2014</start_date>
  <completion_date type="Anticipated">July 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>N/A</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>Beta cell function</measure>
    <time_frame>24 months after treatment phase begins</time_frame>
    <description>Beta cell function will be measured as insulin secretion during the hyperglycemic clamp (mean plasma insulin concentration in uU/ml) multiplied by insulin sensitivity measured with the euglycemic insulin clamp (mg/kg.min).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Insulin sensitivity</measure>
    <time_frame>24 months after treatment phase begins</time_frame>
    <description>Insulin sensitivity will be measured with the euglycemic insulin clamp and expressed as mg/kg.min.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Glucose tolerance status</measure>
    <time_frame>24 months after treatment phase begins</time_frame>
    <description>Glucose tolerance status will be evaluated by measuring the HbA1c which is a measure of the average of the amount of glucose attached to hemoglobin over the past 3 months, expressed as a percentage.</description>
  </primary_outcome>
  <number_of_arms>13</number_of_arms>
  <enrollment type="Anticipated">700</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <condition>Impaired Glucose Tolerance (IGT)</condition>
  <condition>Impaired Fasting Glucose (IFG)</condition>
  <arm_group>
    <arm_group_label>Healthy normal glucose tolerance (NGT) subjects</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subjects (Fasting Plasma Glucose or FPG &lt; 100 mg/dl and 2-h PG &lt; 140 mg/dl) without FH (family history) of diabetes in a first degree relative</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isolated IGT with Dapagliflozin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with isolated IGT (FPG &lt; 100; 2-h PG = 140-199) will receive dapagliflozin, 10 mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isolated IGT with Saxagliptin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with isolated IGT (FPG &lt; 100; 2-h PG = 140-199) will receive saxagliptin, 5 mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isolated IGT with Pioglitazone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with isolated IGT (FPG &lt; 100; 2-h PG = 140-199) will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isolated IGT with Metformin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with isolated IGT (FPG &lt; 100; 2-h PG = 140-199) will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isolated IFG with Dapagliflozin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG &lt; 140) will receive dapagloflozin, 10mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isolated IFG with Saxagliptin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG &lt; 140) will receive saxagliptin, 10mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isolated IFG with Pioglitazone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG &lt; 140) will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isolated IFG with Metformin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG &lt; 140) will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IGT plus IFG with Dapagliflozin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with IGT plus IFG will receive dapagliflozin, 10mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IGT plus IFG with Saxagliptin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with IGT plus IFG will receive saxagliptin, 10mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IGT plus IFG with Pioglitazone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with IGT plus IFG will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IGT plus IFG with Metformin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects with IGT plus IFG will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <description>10mg/day</description>
    <arm_group_label>IGT plus IFG with Dapagliflozin</arm_group_label>
    <arm_group_label>Isolated IFG with Dapagliflozin</arm_group_label>
    <arm_group_label>Isolated IGT with Dapagliflozin</arm_group_label>
    <other_name>farxiga</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saxagliptin</intervention_name>
    <description>5mg/day</description>
    <arm_group_label>IGT plus IFG with Saxagliptin</arm_group_label>
    <arm_group_label>Isolated IFG with Saxagliptin</arm_group_label>
    <arm_group_label>Isolated IGT with Saxagliptin</arm_group_label>
    <other_name>onglyza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pioglitazone</intervention_name>
    <description>the dose will increase from 15 mg/day to 30 mg/day at month two</description>
    <arm_group_label>IGT plus IFG with Pioglitazone</arm_group_label>
    <arm_group_label>Isolated IFG with Pioglitazone</arm_group_label>
    <arm_group_label>Isolated IGT with Pioglitazone</arm_group_label>
    <other_name>actos</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>starting at 1000 mg/day and increased to 2000 mg/day at month 2.</description>
    <arm_group_label>IGT plus IFG with Metformin</arm_group_label>
    <arm_group_label>Isolated IFG with Metformin</arm_group_label>
    <arm_group_label>Isolated IGT with Metformin</arm_group_label>
    <other_name>glucophage</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  NGT subjects will serve as controls and will be matched in age, gender, ethnicity, and&#xD;
             BMI to IGT and IFG subjects&#xD;
&#xD;
               1. Male or female subjects between the ages of 18 and 65 years of age, inclusive, at&#xD;
                  Screening.&#xD;
&#xD;
               2. FPG &lt; 100 mg/dl and 2-h PG &lt; 140 mg/dl&#xD;
&#xD;
               3. BMI = 24-40 kg/m2;&#xD;
&#xD;
               4. Stable body weight (±4lbs) over the preceding 3 months&#xD;
&#xD;
               5. Subjects with no evidence of major organ system disease as determined by physical&#xD;
                  exam, history, and screening laboratory data&#xD;
&#xD;
               6. Females of childbearing potential with a negative pregnancy test at Screening and&#xD;
                  Treatment visits, using one of the following forms of contraception for the&#xD;
                  duration of participation in the study (i.e., until Follow-up 7-14 days post last&#xD;
                  dose):&#xD;
&#xD;
                    -  Oral contraceptive&#xD;
&#xD;
                    -  Injectable progesterone&#xD;
&#xD;
                    -  Subdermal implant&#xD;
&#xD;
                    -  Spermicidal foam/gel/film/cream/suppository&#xD;
&#xD;
                    -  Diaphragm with spermicide&#xD;
&#xD;
                    -  Copper or hormonal containing IUD&#xD;
&#xD;
                    -  Sterile male partner vasectomized &gt; 6 month pre-dosing.&#xD;
&#xD;
               7. Evidence of a personally signed and dated informed consent document indicating&#xD;
                  that the subject has been informed of all pertinent aspects of the study.&#xD;
&#xD;
               8. Subjects must be willing and able to comply with scheduled visits, treatment,&#xD;
                  laboratory tests and study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Recent (i.e., within three (3) months prior to Screening) evidence or medical history&#xD;
             of unstable concurrent disease such as: documented evidence or history of clinically&#xD;
             significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular,&#xD;
             hepatic, psychiatric, immunological, or clinically significant neurological disease.&#xD;
&#xD;
          2. Subjects with a family history of diabetes in a first degree relative&#xD;
&#xD;
          3. BMI of less than 24 or greater than 40 kg/m2&#xD;
&#xD;
          4. Unstable body weight (change of greater than ±4lbs over the preceding 3 months&#xD;
&#xD;
          5. Subjects participating in an excessively heavy exercise program&#xD;
&#xD;
          6. Subject with a feeding/sleeping schedule different from a daytime feeding/night time&#xD;
             sleeping schedule&#xD;
&#xD;
          7. Subjects taking medications known to alter glucose metabolism (with the exception of&#xD;
             metformin and/or pioglitazone) or which effect brain neurosynaptic function are&#xD;
             excluded.&#xD;
&#xD;
          8. Subjects with evidence of major organ system disease as determined by physical exam,&#xD;
             history, and screening laboratory data&#xD;
&#xD;
          9. Pregnant subjects or subjects unwilling to use birth control during their study&#xD;
             enrollment&#xD;
&#xD;
         10. Blood donation of approximately 1 pint (500 mL) within 8 weeks prior to Screening.&#xD;
&#xD;
         11. Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or&#xD;
             investigational product administration or may interfere with the interpretation of&#xD;
             study results and, in the judgment of the investigator, would make the subject&#xD;
             inappropriate for entry into this study&#xD;
&#xD;
         12. Subjects with hematuria will be excluded.&#xD;
&#xD;
         13. Subjects with evidence or prior history of heart failure will be excluded&#xD;
&#xD;
         14. Subjects with family history of pancreatic, bladder, and breast cancer will be&#xD;
             excluded.&#xD;
&#xD;
         15. Subjects with history of pancreatitis will be excluded.&#xD;
&#xD;
         16. Subjects with eGFR &lt; 60 ±5 ml/min.1.73m2 will be excluded.&#xD;
&#xD;
         17. Subjects with elevated serum creatinine (&gt;1.5 mg/dl males/1.4 mg/dl females) will be&#xD;
             excluded.&#xD;
&#xD;
         18. Subjects with a history of orthostatic hypotension (&gt;15/10 mmHg) will be excluded.&#xD;
&#xD;
         19. Subjects with liver enzymes (ALT, AST) &gt;3-fold above upper normal limit will be&#xD;
             excluded.&#xD;
&#xD;
         20. Subjects with a history of hypersensitivity to pioglitazone, dapagliflozin, or&#xD;
             Saxagliptin will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ralph A DeFronzo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Texas Health Science Center at San Antonio</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ralph A DeFronzo, MD</last_name>
    <phone>210-567-6691</phone>
    <email>defronzo@uthscsa.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Monica Palomo, BS</last_name>
    <phone>210-567-6710</phone>
    <email>palomom@uthscsa.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ralph A DeFronzo, MD</last_name>
      <phone>210-567-6691</phone>
      <email>defronzo@uthscsa.edu</email>
    </contact>
    <contact_backup>
      <last_name>Monica Palomo, BS</last_name>
      <phone>210-567-6710</phone>
      <email>palomom@uthscsa.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Ralph A DeFronzo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Eugenio Cersosimo, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>March 16, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <last_update_submitted>August 2, 2023</last_update_submitted>
  <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 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>Prediabetic State</mesh_term>
    <mesh_term>Glucose Intolerance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Pioglitazone</mesh_term>
    <mesh_term>Dapagliflozin</mesh_term>
    <mesh_term>Saxagliptin</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/NCT02969798
org study id: HSC20130414H
secondary id: R01DK024092-34
nct id: NCT02969798
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
HYPOTHESIS: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have distinct
      pathophysiologic etiologies. Therefore, therapeutic interventions designed to correct the
      specific underlying pathogenic abnormalities in IGT and IFG will be required to optimally
      prevent the progressive beta cell failure and development of overt type 2 diabetes.
SPECIFIC AIMS:

        1. To examine the effect of the following pharmacologic interventions on beta cell
           function, insulin sensitivity, and glucose tolerance status in individuals with isolated
           impaired glucose tolerance (IGT): (i) treatment with the renal Sodium-glucose
           co-transporter 2 (SGLT2) inhibitor inhibitor, dapagliflozin; (ii) treatment with the
           inhibitors of dipeptidyl peptidase 4, also DPP4, saxagliptin ; (iii) treatment with the
           thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin.

        2. To examine the effect of the following pharmacologic interventions on beta cell
           function, insulin sensitivity, and glucose tolerance status in individuals with isolated
           impaired fasting glucose (IFG): (i) treatment with the renal SGLT2 inhibitor,
           dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with
           the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin.

        3. To examine the effect of the following pharmacologic interventions on beta cell
           function, insulin sensitivity, and glucose tolerance status in individuals with combined
           impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG): i) treatment with
           the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor,
           saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment
           with the biguanide, metformin.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Beta cell function
time frame: 24 months after treatment phase begins
description: Beta cell function will be measured as insulin secretion during the hyperglycemic clamp (mean plasma insulin concentration in uU/ml) multiplied by insulin sensitivity measured with the euglycemic insulin clamp (mg/kg.min).
measure: Insulin sensitivity
time frame: 24 months after treatment phase begins
description: Insulin sensitivity will be measured with the euglycemic insulin clamp and expressed as mg/kg.min.
measure: Glucose tolerance status
time frame: 24 months after treatment phase begins
description: Glucose tolerance status will be evaluated by measuring the HbA1c which is a measure of the average of the amount of glucose attached to hemoglobin over the past 3 months, expressed as a percentage.
arm group label: Healthy normal glucose tolerance (NGT) subjects
arm group type: No Intervention
description: Subjects (Fasting Plasma Glucose or FPG < 100 mg/dl and 2-h PG < 140 mg/dl) without FH (family history) of diabetes in a first degree relative
arm group label: Isolated IGT with Dapagliflozin
arm group type: Active Comparator
description: Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive dapagliflozin, 10 mg/day
arm group label: Isolated IGT with Saxagliptin
arm group type: Active Comparator
description: Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive saxagliptin, 5 mg/day
arm group label: Isolated IGT with Pioglitazone
arm group type: Active Comparator
description: Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two
arm group label: Isolated IGT with Metformin
arm group type: Active Comparator
description: Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2.
arm group label: Isolated IFG with Dapagliflozin
arm group type: Active Comparator
description: Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive dapagloflozin, 10mg/day
arm group label: Isolated IFG with Saxagliptin
arm group type: Active Comparator
description: Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive saxagliptin, 10mg/day
arm group label: Isolated IFG with Pioglitazone
arm group type: Active Comparator
description: Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two
arm group label: Isolated IFG with Metformin
arm group type: Active Comparator
description: Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2.
arm group label: IGT plus IFG with Dapagliflozin
arm group type: Active Comparator
description: Healthy subjects with IGT plus IFG will receive dapagliflozin, 10mg/day
arm group label: IGT plus IFG with Saxagliptin
arm group type: Active Comparator
description: Healthy subjects with IGT plus IFG will receive saxagliptin, 10mg/day
arm group label: IGT plus IFG with Pioglitazone
arm group type: Active Comparator
description: Healthy subjects with IGT plus IFG will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two
arm group label: IGT plus IFG with Metformin
arm group type: Active Comparator
description: Healthy subjects with IGT plus IFG will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2.
intervention type: Drug
intervention name: Dapagliflozin
description: 10mg/day
arm group label: IGT plus IFG with Dapagliflozin
arm group label: Isolated IFG with Dapagliflozin
arm group label: Isolated IGT with Dapagliflozin
other name: farxiga
intervention type: Drug
intervention name: Saxagliptin
description: 5mg/day
arm group label: IGT plus IFG with Saxagliptin
arm group label: Isolated IFG with Saxagliptin
arm group label: Isolated IGT with Saxagliptin
other name: onglyza
intervention type: Drug
intervention name: Pioglitazone
description: the dose will increase from 15 mg/day to 30 mg/day at month two
arm group label: IGT plus IFG with Pioglitazone
arm group label: Isolated IFG with Pioglitazone
arm group label: Isolated IGT with Pioglitazone
other name: actos
intervention type: Drug
intervention name: Metformin
description: starting at 1000 mg/day and increased to 2000 mg/day at month 2.
arm group label: IGT plus IFG with Metformin
arm group label: Isolated IFG with Metformin
arm group label: Isolated IGT with Metformin
other name: glucophage
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ralph A DeFronzo, MD
role: Principal Investigator
affiliation: The University of Texas Health Science Center at San Antonio
last name: Ralph A DeFronzo, MD
phone: 210-567-6691
email: defronzo@uthscsa.edu
last name: Monica Palomo, BS
phone: 210-567-6710
email: palomom@uthscsa.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Prediabetic State
mesh term: Glucose Intolerance
mesh term: Metformin
mesh term: Pioglitazone
mesh term: Dapagliflozin
mesh term: Saxagliptin