Investigating treatments for pre-diabetes with impaired glucose tolerance and fasting glucose

Preservation of Beta Cell Function in Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)

This study is testing different medications to see if they can help people with pre-diabetes improve their blood sugar levels and prevent them from developing type 2 diabetes.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 700 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: The University of Texas Health Science Center at San Antonio (Academic / other)
• Locations: 1 site (San Antonio, Texas)
• Trial ID: NCT02969798 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effects of various pharmacologic interventions on beta cell function, insulin sensitivity, and glucose tolerance in individuals with impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Participants will receive treatments including dapagliflozin, saxagliptin, pioglitazone, and metformin, tailored to their specific glucose impairment. The study will also include control subjects with normal glucose tolerance matched by age, gender, ethnicity, and BMI. The goal is to identify optimal therapeutic strategies to prevent the progression to type 2 diabetes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with isolated IGT or IFG, or both, and a stable body weight.

Not a fit: Patients with major organ system diseases or those outside the specified age and BMI range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more effective prevention strategies for type 2 diabetes in individuals with pre-diabetes.

How similar studies have performed: Other studies have shown promise in using similar pharmacologic interventions for managing pre-diabetes, indicating potential for success in this approach.

Eligibility criteria

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.

Where this trial is running

San Antonio, Texas

• The University of Texas Health Science Center at San Antonio — San Antonio, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Ralph A DeFronzo, MD — The University of Texas Health Science Center at San Antonio
• Study coordinator: Ralph A DeFronzo, MD

Conditions Diabetes Mellitus, Type 2; Impaired Glucose Tolerance; Impaired Fasting Glucose