Recruiting

Impaired Glucose

Sponsor:

The University of Texas Health Science Center at San Antonio

Code:

NCT02969798

Conditions

Diabetes Mellitus, Type 2

Impaired Glucose Tolerance (IGT)

Impaired Fasting Glucose (IFG)

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Interventions

Dapagliflozin

Saxagliptin

Pioglitazone

Metformin

Study Details

Brief summary:

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.

Conditions

Diabetes Mellitus, Type 2

Impaired Glucose Tolerance (IGT)

Impaired Fasting Glucose (IFG)

Study ID

NCT02969798

Start date

Jan 1, 2014

Status verified date

Aug, 2025

Completion date

Jul, 2027

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Inclusion Criteria:

  • NGT subjects will serve as controls and will be matched in age, gender, ethnicity, and BMI to IGT and IFG subjects

1. Male or female subjects between the ages of 18 and 65 years of age, inclusive, at Screening.
2. FPG < 100 mg/dl and 2-h PG < 140 mg/dl
3. BMI = 24-40 kg/m2;
4. Stable body weight (±4lbs) over the preceding 3 months
5. Subjects with no evidence of major organ system disease as determined by physical exam, history, and screening laboratory data
6. Females of childbearing potential with a negative pregnancy test at Screening and Treatment visits, using one of the following forms of contraception for the duration of participation in the study (i.e., until Follow-up 7-14 days post last dose):

  • Oral contraceptive
  • Injectable progesterone
  • Subdermal implant
  • Spermicidal foam/gel/film/cream/suppository
  • Diaphragm with spermicide
  • Copper or hormonal containing IUD
  • Sterile male partner vasectomized > 6 month pre-dosing.
7. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
8. Subjects must be willing and able to comply with scheduled visits, treatment, laboratory tests and study procedures.

Exclusion Criteria:

1. Recent (i.e., within three (3) months prior to Screening) evidence or medical history of unstable concurrent disease such as: documented evidence or history of clinically significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, immunological, or clinically significant neurological disease.
2. Subjects with a family history of diabetes in a first degree relative
3. BMI of less than 24 or greater than 40 kg/m2
4. Unstable body weight (change of greater than ±4lbs over the preceding 3 months
5. Subjects participating in an excessively heavy exercise program
6. Subject with a feeding/sleeping schedule different from a daytime feeding/night time sleeping schedule
7. Subjects taking medications known to alter glucose metabolism (with the exception of metformin and/or pioglitazone) or which effect brain neurosynaptic function are excluded.
8. Subjects with evidence of major organ system disease as determined by physical exam, history, and screening laboratory data
9. Pregnant subjects or subjects unwilling to use birth control during their study enrollment
10. Blood donation of approximately 1 pint (500 mL) within 8 weeks prior to Screening.
11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
12. Subjects with hematuria will be excluded.
13. Subjects with evidence or prior history of heart failure will be excluded
14. Subjects with family history of pancreatic, bladder, and breast cancer will be excluded.
15. Subjects with history of pancreatitis will be excluded.
16. Subjects with eGFR < 60 ±5 ml/min.1.73m2 will be excluded.
17. Subjects with elevated serum creatinine (>1.5 mg/dl males/1.4 mg/dl females) will be excluded.
18. Subjects with a history of orthostatic hypotension (>15/10 mmHg) will be excluded.
19. Subjects with liver enzymes (ALT, AST) >3-fold above upper normal limit will be excluded.
20. Subjects with a history of hypersensitivity to pioglitazone, dapagliflozin, or Saxagliptin will be excluded.

Study Design

Enrollment

700 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

no intervention: Healthy normal glucose tolerance (NGT) subjects

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

active comparator: Isolated IGT with Dapagliflozin

Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive dapagliflozin, 10 mg/day

active comparator: Isolated IGT with Saxagliptin

Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive saxagliptin, 5 mg/day

active comparator: Isolated IGT with Pioglitazone

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

active comparator: Isolated IGT with Metformin

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.

active comparator: Isolated IFG with Dapagliflozin

Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive dapagloflozin, 10mg/day

active comparator: Isolated IFG with Saxagliptin

Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive saxagliptin, 10mg/day

active comparator: Isolated IFG with Pioglitazone

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

active comparator: Isolated IFG with Metformin

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.

active comparator: IGT plus IFG with Dapagliflozin

Healthy subjects with IGT plus IFG will receive dapagliflozin, 10mg/day

active comparator: IGT plus IFG with Saxagliptin

Healthy subjects with IGT plus IFG will receive saxagliptin, 10mg/day

active comparator: IGT plus IFG with Pioglitazone

Healthy subjects with IGT plus IFG will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two

active comparator: IGT plus IFG with Metformin

Healthy subjects with IGT plus IFG will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2.

Interventions

Dapagliflozin

10mg/day

Saxagliptin

5mg/day

Pioglitazone

the dose will increase from 15 mg/day to 30 mg/day at month two

Metformin

starting at 1000 mg/day and increased to 2000 mg/day at month 2.

Primary outcome measure

  • Beta cell function [ Time Frame: 24 months after treatment phase begins ]
  • Insulin sensitivity [ Time Frame: 24 months after treatment phase begins ]
  • Glucose tolerance status [ Time Frame: 24 months after treatment phase begins ]

Central Contacts and Locations

Central contacts

Locations

The University of Texas Health Science Center at San Antonio

Recruiting

San Antonio, Texas, United States, 78229

Contacts

Principal Investigator:

Ralph A DeFronzo, MD

More Information

Sponsor

The University of Texas Health Science Center at San Antonio

Last update posted

Aug 27, 2025

Last verified

Aug, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by The University of Texas Health Science Center at San Antonio on 2025-08-27.