Impaired Glucose Tolerance, Type 2 Diabetes
Conditions
Keywords
Impaired Glucose Tolerance, Type 2 Diabetes, Prevention, Pioglitazone
Brief summary
The purpose of this study is to examine whether pioglitazone versus placebo can reduce the conversion rate of impaired glucose tolerance (IGT) to type 2 diabetes mellitus
Detailed description
IGT is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, the hyperglycemia-related complications of this devastating disease can be prevented. Subjects with IGT will be identified with an oral glucose tolerance test (OGTT). Eligible subjects also will have a measurement of first phase insulin secretion and insulin sensitivity using the frequently sampled intravenous glucose tolerance test (FSIVGTT) and carotid intimal media thickness using carotid ultrasound. Following these measurements subjects will be randomized to receive pioglitazone or placebo and they will return every 3 months for determination of fasting plasma glucose (FPG) concentration and interim medical history. Recruitment will take place over 15 months. From the time that the recruitment period ends, subjects will be followed for a total of 24 months on pioglitazone or placebo. The OGTT will be repeated at 15,27, and 39 months, or if the FPG is ≥ 126 mg/dl on the 3-month follow up visits. If the diagnosis of diabetes is established before month 39 or at month 39, the FSIVGTT and carotid ultrasound will be repeated. At 39 months, subjects will be washed out of pioglitazone or placebo and the OGTT, FSIVGTT, and carotid ultrasound will be repeated at month 45.
Interventions
DRUGPioglitazone
Pioglitazone tablets - 45 mg/day
DRUGPlacebo
Placebo tablets similar to pioglitazone tablets - 1 tablet/day
Sponsors
University of Texas
Takeda Pharmaceuticals North America, Inc.
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women * All ethnic groups * 18 years of age and older * Impaired glucose tolerance by glucose tolerance test (fasting glucose 95-125 mg/dl and 2 hr glucose of 140-199 mg/dl) * At least one of the following: * One or more components of the insulin resistance syndrome (HDL \< 40 mg/dl in females and \<35 mg/dl in males, fasting triglycerides \> 150 mg/dl, blood pressure \> 135/85 mmHg, BMI \> 24 kg/m2, waist circumference \> 102 cm in men and \> 88 cm in women) * One or more first degree relatives with type 2 diabetes * History of gestational diabetes * Polycystic ovarian disease * Minority ethnic background (Mexican American, African American, Asian and Pacific Islanders, Native American)
Exclusion criteria
* Type 2 diabetes * Previously treated with thiazolidinediones (ever) or metformin (within one year) * Previously treated with a sulfonylurea, a meglitinide, an alpha glucosidase inhibitor for more than a week within last year or within the 3 months prior to randomization * Previously treated with insulin (other than during pregnancy) for more than one week within the last year or within the 3 months prior to randomization * Cardiovascular disease * Hospitalization for treatment of heart disease or stroke in past 6 months * New York Heart Association Functional Class \> 2 * Left bundle branch block or third degree AV block * Aortic stenosis * SBP \> 180 mmHg or DBP \> 105 mmHg * Renal disease * Anemia * Hepatitis * GI diseases (pancreatitis, inflammatory bowel disease) * Recent or significant abdominal surgery * Advanced pulmonary disease * Chronic infections * Weight loss \> 10% in past 6 months * Pregnancy and childbearing * Major psychiatric disorders * Excessive alcohol intake * Thiazide use \> 25 mg per day * Non-selective beta blockers * Niacin * Systemic glucocorticoids * Weight loss or weight gain medication * Thyroid disease-suboptimally treated * Active endocrine diseases (Cushing's, acromegaly) * Plasma triglycerides over 400 mg/dl (despite treatment) * History bladder cancer * Hematuria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevention of Type 2 Diabetes | 2.4 years | Percentage of Participants with Type 2 Diabetes at 2.4 years Post-randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test | Baseline versus 2.4 years | Insulin secretion |
| Change From Baseline in Fasting Plasma Glucose of 2.4 Years | Baseline versus 2.4 years | Fasting Plasma Glucose |
| Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values) | Baseline versus 2.4 years | Insulin sensitivity The Matsuda index was calculated as 10,000/square root of (pre-meal glucose x pre-meal insulin x mean 120 min post-meal glucose x mean 120 min post-meal insulin), with higher numbers indicating better the insulin sensitivity. |
| Change in Atherosclerosis | Baseline versus 2.4 years | carotid intima thickness |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablet similar to pioglitazone tablet
Placebo: Placebo tablets similar to pioglitazone tablets | 299 |
| Pioglitazone Pioglitazone tablet similar to placebo tablet
Pioglitazone: Pioglitazone tablets | 303 |
| Total | 602 |
Baseline characteristics
| Characteristic | Pioglitazone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 32 Participants | 30 Participants | 62 Participants |
| Age, Categorical Between 18 and 65 years | 271 Participants | 269 Participants | 540 Participants |
| Age, Continuous | 52.3 years STANDARD_DEVIATION 0.5 | 52.3 years STANDARD_DEVIATION 0.5 | 52.3 years STANDARD_DEVIATION 0.5 |
| Region of Enrollment United States | 303 participants | 299 participants | 602 participants |
| Sex: Female, Male Female | 127 Participants | 126 Participants | 253 Participants |
| Sex: Female, Male Male | 176 Participants | 173 Participants | 349 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 170 / 299 | 95 / 303 |
| serious Total, serious adverse events | 1 / 299 | 3 / 303 |
Outcome results
Primary
Prevention of Type 2 Diabetes
Percentage of Participants with Type 2 Diabetes at 2.4 years Post-randomization
Time frame: 2.4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Prevention of Type 2 Diabetes | 16.1 percentage of participants |
| Pioglitazone | Prevention of Type 2 Diabetes | 5.0 percentage of participants |
Secondary
Change From Baseline in Fasting Plasma Glucose of 2.4 Years
Fasting Plasma Glucose
Time frame: Baseline versus 2.4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose of 2.4 Years | -4.0 mg/dl | Standard Deviation 0.09 |
| Pioglitazone | Change From Baseline in Fasting Plasma Glucose of 2.4 Years | -10.7 mg/dl | Standard Deviation 0.9 |
Secondary
Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values)
Insulin sensitivity The Matsuda index was calculated as 10,000/square root of (pre-meal glucose x pre-meal insulin x mean 120 min post-meal glucose x mean 120 min post-meal insulin), with higher numbers indicating better the insulin sensitivity.
Time frame: Baseline versus 2.4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values) | 0.7 matsuda index | Standard Deviation 0.2 |
| Pioglitazone | Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values) | 3.6 matsuda index | Standard Deviation 0.2 |
Secondary
Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test
Insulin secretion
Time frame: Baseline versus 2.4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test | 35 nmol | Standard Deviation 5 |
| Pioglitazone | Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test | 25 nmol | Standard Deviation 4 |
Secondary
Change in Atherosclerosis
carotid intima thickness
Time frame: Baseline versus 2.4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Atherosclerosis | 1.7 percentage of intima | Standard Deviation 0.2 |
| Pioglitazone | Change in Atherosclerosis | 3.2 percentage of intima | Standard Deviation 0.2 |