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

NCT02969798 | Recruiting DMC

• 2 other identifiers: HSC20130414HR01DK024092-34
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 1

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)

Outcome Measures

Primary Outcomes (3)

• Beta cell function

  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).

  24 months after treatment phase begins

• Insulin sensitivity

  Insulin sensitivity will be measured with the euglycemic insulin clamp and expressed as mg/kg.min.

  24 months after treatment phase begins

• Glucose tolerance status

  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.

  24 months after treatment phase begins

Study Arms (13)

Healthy normal glucose tolerance (NGT) subjects

NO INTERVENTION

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

Isolated IGT with Dapagliflozin

ACTIVE COMPARATOR

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

Drug: Dapagliflozin

Isolated IGT with Saxagliptin

ACTIVE COMPARATOR

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

Drug: Saxagliptin

Isolated IGT with Pioglitazone

ACTIVE COMPARATOR

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

Isolated IGT with Metformin

ACTIVE COMPARATOR

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

Isolated IFG with Dapagliflozin

ACTIVE COMPARATOR

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

Drug: Dapagliflozin

Isolated IFG with Saxagliptin

ACTIVE COMPARATOR

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

Drug: Saxagliptin

Isolated IFG with Pioglitazone

ACTIVE COMPARATOR

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

Isolated IFG with Metformin

ACTIVE COMPARATOR

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

IGT plus IFG with Dapagliflozin

ACTIVE COMPARATOR

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

Drug: Dapagliflozin

IGT plus IFG with Saxagliptin

ACTIVE COMPARATOR

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

Drug: Saxagliptin

IGT plus IFG with Pioglitazone

ACTIVE COMPARATOR

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

IGT plus IFG with Metformin

ACTIVE COMPARATOR

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

Interventions

Dapagliflozin DRUG

10mg/day

Also known as: farxiga

IGT plus IFG with Dapagliflozin; Isolated IFG with Dapagliflozin; Isolated IGT with Dapagliflozin

Saxagliptin DRUG

5mg/day

Also known as: onglyza

IGT plus IFG with Saxagliptin; Isolated IFG with Saxagliptin; Isolated IGT with Saxagliptin

Pioglitazone DRUG

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

Also known as: actos

IGT plus IFG with Pioglitazone; Isolated IFG with Pioglitazone; Isolated IGT with Pioglitazone

Metformin DRUG

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

Also known as: glucophage

IGT plus IFG with Metformin; Isolated IFG with Metformin; Isolated IGT with Metformin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• NGT subjects will serve as controls and will be matched in age, gender, ethnicity, and BMI to IGT and IFG subjects
• Male or female subjects between the ages of 18 and 65 years of age, inclusive, at Screening.
• FPG \< 100 mg/dl and 2-h PG \< 140 mg/dl
• BMI = 24-40 kg/m2;
• Stable body weight (±4lbs) over the preceding 3 months
• Subjects with no evidence of major organ system disease as determined by physical exam, history, and screening laboratory data
• 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.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

You may not qualify if:

• 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.
• Subjects with a family history of diabetes in a first degree relative
• BMI of less than 24 or greater than 40 kg/m2
• Unstable body weight (change of greater than ±4lbs over the preceding 3 months
• Subjects participating in an excessively heavy exercise program
• Subject with a feeding/sleeping schedule different from a daytime feeding/night time sleeping schedule
• Subjects taking medications known to alter glucose metabolism (with the exception of metformin and/or pioglitazone) or which effect brain neurosynaptic function are excluded.
• Subjects with evidence of major organ system disease as determined by physical exam, history, and screening laboratory data
• Pregnant subjects or subjects unwilling to use birth control during their study enrollment
• Blood donation of approximately 1 pint (500 mL) within 8 weeks prior to Screening.
• 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
• Subjects with hematuria will be excluded.
• Subjects with evidence or prior history of heart failure will be excluded
• Subjects with family history of pancreatic, bladder, and breast cancer will be excluded.
• Subjects with history of pancreatitis will be excluded.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• American Diabetes Association: collaborator
• AstraZeneca: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Glucose Intolerance

Interventions

dapagliflozin; saxagliptin; Pioglitazone; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

Study Officials

• Ralph A DeFronzo, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ralph A DeFronzo, MD

CONTACT

210-567-6691; defronzo@uthscsa.edu

Monica Palomo, BS

CONTACT

210-567-6710; palomom@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: November 21, 2016
• Study Start: January 1, 2014
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 27, 2025

Record last verified: 2025-08

Locations

US (1)