Find-A-Study

Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)

Purpose

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.

Study Contact

Principal Investigator
Ralph DeFronzo

Renata Belfort De Aguiar
210-450-3076
belfortda@uthscsa.edu

Alberto Chavez-Velazquez
210-358-7200
chavezvelazq@uthscsa.edu

Andrea Hansis-Diarte
210-567-3208
hansisdiarte@uthscsa.edu

Aurora Merovci
210-567-6691
merovci@uthscsa.edu

Cynthia Ramirez
210-358-7200
ramirezc8@uthscsa.edu

Eligibility

Eligible Ages: Between 18 Years and 65 Years
Eligible Genders: All
Accepts Healthy Volunteers: Yes

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

Phase: N/A
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)
Condition: Diabetes Mellitus, Type 2
Impaired Glucose Tolerance (IGT)
Impaired Fasting Glucose (IFG)

Arm Groups

Arm	Description	Intervention
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 Saxagliptin	Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive saxagliptin, 5 mg/day	Drug: Saxagliptin 5mg/day Other names: onglyza
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.	Drug: Metformin starting at 1000 mg/day and increased to 2000 mg/day at month 2. Other names: glucophage
Active Comparator Isolated IFG with Saxagliptin	Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive saxagliptin, 10mg/day	Drug: Saxagliptin 5mg/day Other names: onglyza
Active Comparator Isolated IGT with Dapagliflozin	Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive dapagliflozin, 10 mg/day	Drug: Dapagliflozin 10mg/day Other names: farxiga
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	Drug: Pioglitazone the dose will increase from 15 mg/day to 30 mg/day at month two Other names: actos
Active Comparator Isolated IFG with Dapagliflozin	Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive dapagloflozin, 10mg/day	Drug: Dapagliflozin 10mg/day Other names: farxiga
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	Drug: Pioglitazone the dose will increase from 15 mg/day to 30 mg/day at month two Other names: actos
Active Comparator IGT plus IFG with Dapagliflozin	Healthy subjects with IGT plus IFG will receive dapagliflozin, 10mg/day	Drug: Dapagliflozin 10mg/day Other names: farxiga
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	Drug: Pioglitazone the dose will increase from 15 mg/day to 30 mg/day at month two Other names: actos
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.	Drug: Metformin starting at 1000 mg/day and increased to 2000 mg/day at month 2. Other names: glucophage
Active Comparator IGT plus IFG with Saxagliptin	Healthy subjects with IGT plus IFG will receive saxagliptin, 10mg/day	Drug: Saxagliptin 5mg/day Other names: onglyza
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.	Drug: Metformin starting at 1000 mg/day and increased to 2000 mg/day at month 2. Other names: glucophage