Insulin Resistance, Metabolic Syndrome, Type 2 Diabetes
Conditions
Keywords
Inflammatory cytokine, Cardiovascular Disease, Thrombotic factors, Dyslipidemia
Brief summary
The objective of this study is to determine whether targeted pharmacological improvement of insulin sensitivity will normalize the associated elevations of thrombotic and inflammatory cardiovascular disease (CVD) biomarkers in individuals with insulin resistance.
Detailed description
Individuals with diabetes mellitus (DM) are disproportionately affected by atherothrombotic disorders, including cardiovascular, cerebrovascular, and peripheral vascular diseases. Atherothrombotic disease risk and mortality are also increased with metabolic syndrome, a constellation of risk factors present in more than 34% of adults, even in absence of diabetes. Yet, large clinical trials of diabetes therapies have shown that conventional cardiovascular disease (CVD) risk factors, specifically hyperglycemia and hypertension, do not fully account for increased CVD risk associated with DM. There may be an etiologic link among insulin resistance, inflammation and thrombotic events. This study seeks to determine if certain two diabetes medications (the insulin sensitizing medications) will affect certain biomarkers (or laboratory tests) for CVD in individuals with untreated DM or impaired fasting glucose. Patients will be screened for inclusion into this this double-blinded, randomized), placebo-controlled study. If inclusion criteria are met and exclusion criteria not met, patients will be enrolled in the the study. Half of the subjects will be randomized (like the flip of a coin) to take two insulin sensitizing, anti-diabetic drugs pioglitazone (Actos) and metformin (Glucophage) taken together for three months and the other half of the subjects will take corresponding placebo (dummy) tablets. Laboratory measurements will be obtained on the morning(s) following the two in-patient overnight stays in the Mayo Clinic Clinical Research Unit. The first stay will be at baseline and the second stay will be 3 months after baseline. Insulin sensitivity will be measured in the morning following a standardized meal the preceding night, and after an overnight fast. The changes (from baseline to 3 months) in insulin sensitivity, glycemic control, the lipid profile, thrombotic markers and inflammatory markers will be determined and compared between the two arms of the study (placebo versus insulin sensitizing drugs).
Interventions
DRUGmetformin
To minimize side effects the metformin will be initiated at 500 mg twice daily with meals and increased to 1 gm twice daily with meals after two weeks and continue to a total of 3 months of dosing.
DRUGpioglitazone
To minimize side effects, the pioglitazone will be initiated at 30 mg daily and increased to 45 mg daily after two weeks, and continue to a total of 3 months of dosing.
DRUGPlacebo
Placebo tablets matching the metformin and pioglitazone tablets are given in the same regimen as the active drug arm for 3 months.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Takeda Pharmaceuticals North America, Inc.
National Center for Research Resources (NCRR)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* We will study 30 patients with Type 2 Diabetes or impaired fasting glucose (15 men & 15 women) who are \> 20 years old. * Only patients who use lifestyle modification to manage their diabetes and are not on any oral hypoglycemic agents or insulin will be included. * We will enroll subjects who have fasting glucose concentration greater than 100 mg/dl on two consecutive occasions and have a Body Mass Index between 27-36 kg/m\^2.
Exclusion criteria
* We will exclude patients whose blood glucose is above 180 mg/dl. This will avoid the need to perform home glucose monitoring and the potential of unblinding the study by the volunteers. * Patients taking oral hypoglycemic agents or insulin would be excluded. * Any diseases such as active cardiovascular disease, liver diseases, kidney failure (males with serum creatinine \>= 1.5mg/dl, females \>=1.4 mg/dl), active endocrinopathies, debilitating chronic disease, anemia, symptoms of undiagnosed illness, history of alcoholism (alcohol use \> 4oz/day) or substance abuse, chronic neurological diseases including Alzheimer's disease, stroke, etc, myopathies or any other active disease that may potentially affect the outcome measures. * Patients on medicines such as beta blockers, corticosteroids, tricyclics, benzodiazepines, opiates, barbiturates, anticoagulants and any other drugs or preparations that may affect mitochondrial function will be excluded. * People allergic to any of the class of drug such as lidocaine will also be excluded. * People with pacemakers, certain aneurysm clips and claustrophobia will also be excluded as they cannot undergo magnetic resonance imaging.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR) | Baseline, 3 months | Insulin sensitivity was measured the morning after an overnight fast during an in-patient stay in the Clinical Research Unit & was determined by the mean GIR necessary to maintain euglycemia during a hyperinsulinemic (1.5 mcIU/kg of FFM per minute)-euglycemic (85-95 mg/dL) clamp. The clamp is an 8 hour process where a hand vein is catheterized to collect blood samples and intravenous lines are used to infuse glucose, saline, insulin, phenylalanine and amino acid solutions at at pre-specified times/rates. The mean GIR was calculated as the rate per kilograms of fat-free mass (FFM) during 4 hours of steady-state (hours 4-8 of the 8 hour clamp) reported as micromols/kilogram of FFM per minute. The FFM was measured by dual-energy x-ray absorptiometry (DEXA) scan. Insulin was infused with 5% essential amino acid solution (3mL/kg of FFM/hour) to prevent the insulin-dependent decrease of amino acids during insulin infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lipid Profile | Baseline, 3 months | Change in lipids were measured by the change from baseline to 3 months of triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). All were reported in milligrams/deciliter (mg/dL). |
| Change From Baseline in the Inflammatory Biomarker Interleukin 6 (IL-6) | Baseline, 3 months | IL-6 is an inflammatory cytokine and reported in picograms per deciliter (pg/dL). |
| Change From Baseline in the Inflammatory Biomarker C-Reactive Protein (CRP) | Baseline, 3 months | CRP is an inflammatory cytokine and is reported in milligrams per deciliter (mg/dL). |
| Change From Baseline in Inflammatory Biomarker Tumor Necrosis Factor-alpha (TNF-α) | Baseline, 3 month | TNF-α is an inflammatory cytokine and is reported in picograms/milliliter (pg/mL). |
| Change From Baseline in the Inflammatory Biomarker Adiponectin | Baseline, 3 months | Adiponectin is an anti-inflammatory cytokine and is reported in milligrams per milliliter (mg/mL). |
| Change From Baseline in Fasting Blood Glucose Level | Baseline, 3 months | Glucose (sugar) was measured in the blood and reported in milligrams per deciliter (mg/dL). |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline, 3 months | HbA1c is a measure of average blood sugar levels over the preceding 3 month period. HbA1c was measured by ion-exchange chromatography and reported as a percentage. |
| Change From Baseline in Insulin Levels | Baseline, 3 months | Insulin levels in the blood were measured by immunoenzymatic assay and reported in micro International Units per milliliter (mcIU/mL). |
| Change From Baseline in the Thrombotic Biomarker Fibrinogen | Baseline, 3 months | Fibrinogen was measured by thrombin clotting rate assay (Beckman Coulter, Inc. Brea, California) and reported in milligrams/deciliter (mg/dL). |
| Change From Baseline in the Thrombotic Biomarker Plasminogen Activator Inhibitor-1 (PAI-1) | Baseline, 3 months | PAI-1 was measured by enzyme-linked immunosorbent assay (Diagnostica Stago Inc., Parsippany, New Jersey) and reported in nanograms per milliliter (ng/mL). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fat-Free Mass (FFM) | Baseline, 3 months | FFM was measured using dual energy x-ray absorptiometry (DEXA) scans and is reported in kilograms (kg). |
| Change From Baseline in Body Mass Index | Baseline, 3 months | Body Mass Index (BMI) is a health index for comparing weight to height. BMI is a person's weight in kilograms (kg) divided by his or her height in meters squared. The body mass index is an indication if a person is at a suitable weight for his height on an approximation of body fat. |
| Change From Baseline in Body Fat | Baseline, 3 months | Body fat is reported as a percentage of body weight. |
Countries
United States
Participant flow
Recruitment details
The study was conducted between 8/19/2005 and 8/24/2010 at the Mayo Clinic in Rochester, Minnesota.
Pre-assignment details
48 Northern European Americans were assessed for eligibility and of those, 20 did not meet inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Sensitizer Therapy Two insulin sensitizing drugs will be taken together for 3 months; metformin 1000 mg twice daily plus pioglitazone 45 mg daily. The number of subjects analyzed for baseline measures and outcome measures were the 12 subjects who completed the study. | 12 |
| Placebo Placebo tablets were used to match the active comparator drugs and dosing regimen. The number of subjects analyzed for baseline measures and outcome measures were the 13 subjects who completed the study. | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Insulin Sensitizer Therapy |
|---|---|---|---|
| Adiponectin | 5.63 milligrams per milliliter STANDARD_DEVIATION 2.15 | 5.22 milligrams per milliliter STANDARD_DEVIATION 2.13 | 6.08 milligrams per milliliter STANDARD_DEVIATION 2.17 |
| Age Continuous | 52.4 years STANDARD_DEVIATION 16.6 | 52.2 years STANDARD_DEVIATION 18.2 | 52.5 years STANDARD_DEVIATION 15.6 |
| Body Fat | 44.81 Percentage of body weight STANDARD_DEVIATION 7.8 | 43.26 Percentage of body weight STANDARD_DEVIATION 9.17 | 46.49 Percentage of body weight STANDARD_DEVIATION 5.92 |
| Body Mass Index | 31.00 kilograms/m^2 STANDARD_DEVIATION 4.71 | 29.67 kilograms/m^2 STANDARD_DEVIATION 3.34 | 32.43 kilograms/m^2 STANDARD_DEVIATION 5.65 |
| C-Reactive Protein (CRP) | 0.42 milligrams per deciliter STANDARD_DEVIATION 0.45 | 0.43 milligrams per deciliter STANDARD_DEVIATION 0.49 | 0.42 milligrams per deciliter STANDARD_DEVIATION 0.43 |
| Fasting Blood Glucose | 127.68 milligrams per deciliter STANDARD_DEVIATION 23.82 | 129.00 milligrams per deciliter STANDARD_DEVIATION 26.32 | 126.25 milligrams per deciliter STANDARD_DEVIATION 21.87 |
| Fat-Free Mass | 47.70 Kilograms STANDARD_DEVIATION 13.66 | 46.67 Kilograms STANDARD_DEVIATION 13.54 | 48.81 Kilograms STANDARD_DEVIATION 14.29 |
| Fibrinogen | 406.80 milligrams per deciliter STANDARD_DEVIATION 89.57 | 418.92 milligrams per deciliter STANDARD_DEVIATION 100.23 | 393.67 milligrams per deciliter STANDARD_DEVIATION 78.63 |
| Glucose Infusion Rate (GIR) | 22.86 micromols/kilogram of FFM/minute STANDARD_DEVIATION 14.68 | 23.40 micromols/kilogram of FFM/minute STANDARD_DEVIATION 15.27 | 22.28 micromols/kilogram of FFM/minute STANDARD_DEVIATION 14.67 |
| Glycosylated Hemoglobin (HbA1c) | 6.11 Percentage STANDARD_DEVIATION 0.68 | 6.25 Percentage STANDARD_DEVIATION 0.65 | 5.97 Percentage STANDARD_DEVIATION 0.71 |
| Insulin level | 12.82 micro International Units per milliliter STANDARD_DEVIATION 8.23 | 10.18 micro International Units per milliliter STANDARD_DEVIATION 5.7 | 15.68 micro International Units per milliliter STANDARD_DEVIATION 9.75 |
| Interleukin-6 (IL-6) | 2.88 picograms per milliliter STANDARD_DEVIATION 3.59 | 3.28 picograms per milliliter STANDARD_DEVIATION 4.79 | 2.46 picograms per milliliter STANDARD_DEVIATION 1.68 |
| Lipid Profile High Density Lipoprotein-Cholesterol (HDL-C) | 41.20 milligrams per deciliter STANDARD_DEVIATION 10.84 | 39.23 milligrams per deciliter STANDARD_DEVIATION 8.74 | 43.33 milligrams per deciliter STANDARD_DEVIATION 12.78 |
| Lipid Profile Non-HDL-Cholesterol | 133.96 milligrams per deciliter STANDARD_DEVIATION 23.47 | 132.46 milligrams per deciliter STANDARD_DEVIATION 21.65 | 135.58 milligrams per deciliter STANDARD_DEVIATION 26.17 |
| Lipid Profile Triglycerides | 133.28 milligrams per deciliter STANDARD_DEVIATION 51.93 | 135.00 milligrams per deciliter STANDARD_DEVIATION 51.36 | 131.42 milligrams per deciliter STANDARD_DEVIATION 54.76 |
| Plasminogen Activator Inhibitor 1 (PAI-1) | 68.3 nanograms per milliliter STANDARD_DEVIATION 31.1 | 55.85 nanograms per milliliter STANDARD_DEVIATION 33.7 | 81.83 nanograms per milliliter STANDARD_DEVIATION 22.01 |
| Region of Enrollment United States | 25 participants | 13 participants | 12 participants |
| Sex: Female, Male Female | 15 Participants | 8 Participants | 7 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 5 Participants |
| Tumor Necrosis Factor-alpha (TNF-α) | 2.22 picograms per milliliter STANDARD_DEVIATION 3.91 | 2.98 picograms per milliliter STANDARD_DEVIATION 5.39 | 1.39 picograms per milliliter STANDARD_DEVIATION 0.57 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 |
Outcome results
Primary
Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR)
Insulin sensitivity was measured the morning after an overnight fast during an in-patient stay in the Clinical Research Unit & was determined by the mean GIR necessary to maintain euglycemia during a hyperinsulinemic (1.5 mcIU/kg of FFM per minute)-euglycemic (85-95 mg/dL) clamp. The clamp is an 8 hour process where a hand vein is catheterized to collect blood samples and intravenous lines are used to infuse glucose, saline, insulin, phenylalanine and amino acid solutions at at pre-specified times/rates. The mean GIR was calculated as the rate per kilograms of fat-free mass (FFM) during 4 hours of steady-state (hours 4-8 of the 8 hour clamp) reported as micromols/kilogram of FFM per minute. The FFM was measured by dual-energy x-ray absorptiometry (DEXA) scan. Insulin was infused with 5% essential amino acid solution (3mL/kg of FFM/hour) to prevent the insulin-dependent decrease of amino acids during insulin infusion.
Time frame: Baseline, 3 months
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR) | 17.95 micromols/kg of FFM/minute | Standard Deviation 8.6 |
| Placebo | Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR) | 1.68 micromols/kg of FFM/minute | Standard Deviation 7.56 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Fasting Blood Glucose Level
Glucose (sugar) was measured in the blood and reported in milligrams per deciliter (mg/dL).
Time frame: Baseline, 3 months
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in Fasting Blood Glucose Level | -19.96 mg/dL | Standard Deviation 14.02 |
| Placebo | Change From Baseline in Fasting Blood Glucose Level | 8.39 mg/dL | Standard Deviation 22.51 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
HbA1c is a measure of average blood sugar levels over the preceding 3 month period. HbA1c was measured by ion-exchange chromatography and reported as a percentage.
Time frame: Baseline, 3 months
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | -0.35 percentage | Standard Deviation 0.4 |
| Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 0.19 percentage | Standard Deviation 0.6 |
p-value: 0.02Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Inflammatory Biomarker Tumor Necrosis Factor-alpha (TNF-α)
TNF-α is an inflammatory cytokine and is reported in picograms/milliliter (pg/mL).
Time frame: Baseline, 3 month
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in Inflammatory Biomarker Tumor Necrosis Factor-alpha (TNF-α) | -0.13 pg/mL | Standard Deviation 0.21 |
| Placebo | Change From Baseline in Inflammatory Biomarker Tumor Necrosis Factor-alpha (TNF-α) | 0.18 pg/mL | Standard Deviation 0.37 |
p-value: 0.02Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Insulin Levels
Insulin levels in the blood were measured by immunoenzymatic assay and reported in micro International Units per milliliter (mcIU/mL).
Time frame: Baseline, 3 months
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in Insulin Levels | -8.13 microIU/mL | Standard Deviation 7.47 |
| Placebo | Change From Baseline in Insulin Levels | 1.38 microIU/mL | Standard Deviation 3.29 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Lipid Profile
Change in lipids were measured by the change from baseline to 3 months of triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). All were reported in milligrams/deciliter (mg/dL).
Time frame: Baseline, 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in Lipid Profile | Triglycerides | -15.58 mg/dL | Standard Deviation 32.67 |
| Insulin Sensitizer Therapy | Change From Baseline in Lipid Profile | HDL-C-Cholesterol | 4.33 mg/dL | Standard Deviation 6.75 |
| Insulin Sensitizer Therapy | Change From Baseline in Lipid Profile | Non-HDL-Cholesterol | -7.50 mg/dL | Standard Deviation 15.29 |
| Placebo | Change From Baseline in Lipid Profile | Non-HDL-Cholesterol | 4.62 mg/dL | Standard Deviation 17.76 |
| Placebo | Change From Baseline in Lipid Profile | Triglycerides | 17.77 mg/dL | Standard Deviation 28.86 |
| Placebo | Change From Baseline in Lipid Profile | HDL-C-Cholesterol | -0.31 mg/dL | Standard Deviation 3.9 |
Comparison: P-value is for comparison between groups of the mean change in triglyceride levels.p-value: 0.03Wilcoxon (Mann-Whitney)
Comparison: P-value is for comparison between groups of the mean change in HDL-C levels.p-value: 0.06Wilcoxon (Mann-Whitney)
Comparison: P-value is for comparison between groups of mean change in non-HDL-C levels.p-value: 0.06Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in the Inflammatory Biomarker Adiponectin
Adiponectin is an anti-inflammatory cytokine and is reported in milligrams per milliliter (mg/mL).
Time frame: Baseline, 3 months
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in the Inflammatory Biomarker Adiponectin | 9.10 mg/mL | Standard Deviation 5.22 |
| Placebo | Change From Baseline in the Inflammatory Biomarker Adiponectin | 0.46 mg/mL | Standard Deviation 0.92 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in the Inflammatory Biomarker C-Reactive Protein (CRP)
CRP is an inflammatory cytokine and is reported in milligrams per deciliter (mg/dL).
Time frame: Baseline, 3 months
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in the Inflammatory Biomarker C-Reactive Protein (CRP) | -0.19 mg/dL | Standard Deviation 0.22 |
| Placebo | Change From Baseline in the Inflammatory Biomarker C-Reactive Protein (CRP) | -0.15 mg/dL | Standard Deviation 0.53 |
p-value: 0.05Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in the Inflammatory Biomarker Interleukin 6 (IL-6)
IL-6 is an inflammatory cytokine and reported in picograms per deciliter (pg/dL).
Time frame: Baseline, 3 months
Population: Per protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in the Inflammatory Biomarker Interleukin 6 (IL-6) | -0.99 pg/mL | Standard Deviation 1.44 |
| Placebo | Change From Baseline in the Inflammatory Biomarker Interleukin 6 (IL-6) | -1.42 pg/mL | Standard Deviation 4.84 |
p-value: 0.13Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in the Thrombotic Biomarker Fibrinogen
Fibrinogen was measured by thrombin clotting rate assay (Beckman Coulter, Inc. Brea, California) and reported in milligrams/deciliter (mg/dL).
Time frame: Baseline, 3 months
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in the Thrombotic Biomarker Fibrinogen | 14.00 mg/dL | Standard Deviation 71.24 |
| Placebo | Change From Baseline in the Thrombotic Biomarker Fibrinogen | -18.62 mg/dL | Standard Deviation 62.91 |
p-value: 0.23Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in the Thrombotic Biomarker Plasminogen Activator Inhibitor-1 (PAI-1)
PAI-1 was measured by enzyme-linked immunosorbent assay (Diagnostica Stago Inc., Parsippany, New Jersey) and reported in nanograms per milliliter (ng/mL).
Time frame: Baseline, 3 months
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in the Thrombotic Biomarker Plasminogen Activator Inhibitor-1 (PAI-1) | -34.17 ng/mL | Standard Deviation 25.35 |
| Placebo | Change From Baseline in the Thrombotic Biomarker Plasminogen Activator Inhibitor-1 (PAI-1) | 8.15 ng/mL | Standard Deviation 30.78 |
p-value: 0.002Wilcoxon (Mann-Whitney)
Other Pre-specified
Change From Baseline in Body Fat
Body fat is reported as a percentage of body weight.
Time frame: Baseline, 3 months
Population: Per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in Body Fat | 1.73 percentage of body weight | Standard Deviation 3.08 |
| Placebo | Change From Baseline in Body Fat | -0.01 percentage of body weight | Standard Deviation 1.44 |
p-value: 0.18Wilcoxon (Mann-Whitney)
Other Pre-specified
Change From Baseline in Body Mass Index
Body Mass Index (BMI) is a health index for comparing weight to height. BMI is a person's weight in kilograms (kg) divided by his or her height in meters squared. The body mass index is an indication if a person is at a suitable weight for his height on an approximation of body fat.
Time frame: Baseline, 3 months
Population: Per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in Body Mass Index | 0.37 kg/m^2 | Standard Deviation 0.62 |
| Placebo | Change From Baseline in Body Mass Index | -0.21 kg/m^2 | Standard Deviation 0.4 |
p-value: 0.006Wilcoxon (Mann-Whitney)
Other Pre-specified
Change From Baseline in Fat-Free Mass (FFM)
FFM was measured using dual energy x-ray absorptiometry (DEXA) scans and is reported in kilograms (kg).
Time frame: Baseline, 3 months
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Sensitizer Therapy | Change From Baseline in Fat-Free Mass (FFM) | -1.13 kilograms | Standard Deviation 2.81 |
| Placebo | Change From Baseline in Fat-Free Mass (FFM) | -0.34 kilograms | Standard Deviation 1.28 |
p-value: 0.76Wilcoxon (Mann-Whitney)