Atherosclerosis
Conditions
Keywords
atheroma, IVUS, Intravascular ultrasound, atherosclerosis
Brief summary
The purpose of this study is to test the safety and effectiveness of rosiglitazone against a sulfonylurea in reducing or slowing the development of atherosclerosis in the blood vessels of the heart.
Interventions
DRUGGlipizide
oral anti-diabetic medication
oral antidiabetic medication
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female between 30 to 80 years of age, inclusive. * Established diagnosis of T2DM (based on diagnostic criteria of the American Diabetes Association (ADA), WHO guidelines or local national guidelines). * Subjects who are undergoing coronary angiography for evaluation of suspected or previously diagnosed coronary artery disease or who are undergoing PCI. * Subjects' prior anti-hyperglycemic diabetic therapy: Diet and exercise only (drug naïve), with HbA1c \>7.0 and £ 10.0%. HbA1c \> 6.5 and \<= 8.5%. * Left ventricular ejection fraction (EF) ³ 40% as assessed by contrast ventriculography (or previously documented in medical notes within one month prior to index procedure by other methods e.g. echocardiography or nuclear study) * Female subjects must be postmenopausal (i.e., \>6 months without menstrual period), surgically sterile, or using effective contraceptive measures (oral contraceptives, Norplant, Depo-Provera, an intra-uterine device (IUD), a diaphragm with spermicide or a condom with spermicide). Women of childbearing potential must use effective contraceptive measures for at least 1 month prior to visit 1a, and should continue to use the same contraceptive method during the study and for 30 days after discontinuing study medication. * Willingness and ability to give informed consent prior to entering the study and available to complete the study.
Exclusion criteria
* Type 1 diabetes and/or history of diabetic ketoacidosis. * Exposure to a TZD or other PPAR-g agonist within the 6 months prior to screening visit. * Subjects treated with triple OAD therapy or high dose dual combination OAD therapy \[1\]. * Subjects who have required chronic insulin use in the last 6 months (except during pregnancy or acute episodes such as hospitalization, trauma or infection). * ST segment elevation myocardial infarction in the last 30 days. * Subjects who have a history or are scheduled to receive coronary artery bypass graft surgery (CABG), valve repair or replacement, aneurysmectomy or planned major non-cardiac surgery during the study period. * Subjects who have severe cardiac valvular disease * Stroke or resuscitated in the past 6 months * History of congestive heart failure (NYHA class I - IV) * History of significant hypersensitivity or reaction (e.g., difficulty swallowing, difficulty breathing, tachycardia or skin reaction) to any TZD, SU, biguanide or insulin * Prior history of severe edema or edema requiring medical treatment. * Chronic disease requiring chronic or intermittent treatment with oral, intravenous, or injected corticosteroids (use of topical, inhaled, or nasal corticosteroids is permissible). * Recent history or suspicion of current drug abuse or alcohol abuse within the last 6 months. * Untreated hypo- or hyperthyroidism * A diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or adequately treated cervical carcinoma in situ) in the past 3 years or current treatment for the active cancer. * Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgement of the Investigator, would preclude safe completion of the study. * Blood pressure: SBP \>170 or DBP \> 100 mmHg * Significant anemia (Hemoglobin \< 11 g/dL for males and \< 10 g/dL for females). * Significant renal disease manifested by serum creatinine (\> 1.5mg/dL for males or \> 1.4mg/dL for females), or where the use of metformin is contra-indicated. * Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST \> 2.5 times upper limit of normal (ULN) or bilirubin \>2x ULN). * History of myopathy or history of elevated creatine kinase (CK) \> 3 times upper normal limit. * Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer). * Women who are lactating, pregnant or planning to become pregnant during the course of the study. * Unwillingness or inability to comply with the procedures described in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percent Atheroma Volume (PAV) to Month 18 | Baseline to Month 18 | The primary efficacy endpoint was change in PAV (defined as total atheroma volume divided by total vessel volume x 100) within a 40 mm segment in non-intervened coronary arteries from Baseline to Month 18, based upon Intravascular Ultrasound (IVUS) assessment. |
| Model Adjusted Change From Baseline in Percent Atheroma Volume (PAV) to Month 18 | Baseline to Month 18 | Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior Oral Anti-Hyperglycemic Diabetic Medications(s) (OAD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Model Adjusted Change From Baseline in Lumen Volume to Month 18 | Baseline to Month 18 | IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication. |
| Model Adjusted Change From Baseline in Vessel Volume to Month 18 | Baseline to Month 18 | IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication. |
| Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Baseline to Month 18 | IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18 |
| Model Adjusted Change From Baseline in Atheroma Area to Month 18 | Baseline to Month 18 | IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication. |
| Model Adjusted Change From Baseline in Lumen Area to Month 18 | Baseline to Month 18 | IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication. |
| Model Adjusted Change From Baseline in Vessel Area to Month 18 | Baseline to Month 18 | IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication. |
| Change From Baseline in Normalized Atheroma Volume | Baseline to Month 18 | IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Normalized atheroma volume is defined as mean atheroma area x median segment length in cohort. |
| Model Adjusted Change From Baseline in Normalized Atheroma Volume | Baseline to Month 18 | IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Normalized atheroma volume is defined as mean atheroma area x median segment length in cohort. Model Adjusted Change = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication. |
| Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Baseline to Month 18 | IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area |
| Model Adjusted Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Baseline to Month 18 | IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area. Model Adjusted Change = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication. |
| Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Baseline to Month 18 | IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area |
| Model Adjusted Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Baseline to Month 18 | IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area. Model Adjusted Change = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication. |
| Model Adjusted Change in Glycated Hemoglobin (HbA1c) From Baseline to Month 18 | Baseline to Month 18 | From repeated measures analysis model: Change = Baseline + visit + sex + region + treatment + prior Oral Anti-Hyperglycemic Diabetic Medications(s) (OAD) + cardiac procedure + treatment x visit. |
| Model Adjusted Change in Fasting Plasma Glucose (FPG) From Baseline to Month 18 | Baseline to Month 18 | From repeated measures analysis model: Change = Baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Repeated Measures Analysis of Percent Change in hsCRP From Baseline to Month 18 | Baseline to Month 18 | Changes in cardiovascular biomarkers from Baseline to Month 18, such as high sensitivity C-reactive protein (hsCRP) . Repeated measures analysis model: Log(value) - log(baseline) = log(baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Repeated Measures Analysis of Percent Change in MMP 9 From Baseline to Month 18 | Baseline to Month 18 | Changes in cardiovascular biomarkers from Baseline to Month 18, such as matrix metalloproteinase-9 (MMP-9). Repeated measures analysis model: Log(value) - log(baseline) = log(baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Baseline to Month 18 | IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18 |
| Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Baseline to Month 18 | It was measured as ratio to baseline as percentage change based on log-transformed data : 100 x (exp(Mean change on log scale) - 1). Model Adjusted change based on ANCOVA: Log(value) - log(Baseline) = log(Baseline) + sex + region + treatment + prior OAD + cardiac procedure. |
| Percent Change From Baseline to Month 18 in Total Cholesterol (TC) | Baseline to Month 18 | Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Percent Change From Baseline to Month 18 in High Density Lipoprotein Cholesterol (HDL-c) | Baseline to Month 18 | Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Percent Change From Baseline to Month 18 in HDL-2 | Baseline to Month 18 | Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Percent Change From Baseline to Month 18 in HDL-3 | Baseline to Month 18 | Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Percent Change From Baseline to Month 18 in Low Density Lipoprotein Cholesterol (LDL-c) | Baseline to Month 18 | Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Percent Change From Baseline to Month 18 in Triglycerides (TG) | Baseline to Month 18 | Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Percent Change From Baseline to Month 18 in Free Fatty Acids (FFA) | Baseline to Month 18 | Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Percent Change From Baseline to Month 18 in Apoprotein B (apoB) | Baseline to Month 18 | Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Change From Baseline to Month 18 in LDL-c Peak Particle Density Measured by LDL Relative Flotation | Baseline to Month 18 | From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Change From Baseline to Month 18 in Total Cholesterol/HDL-c Ratio | Baseline to Month 18 | From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Change From Baseline to Month 18 in LDL-c/HDL-c Ratio | Baseline to Month 18 | From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit. |
| Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for All-cause Death, Non-fatal MI, Non-fatal Stroke, Coronary Revascularization, or Hospitalization for Recurrent Myocardial Ischemia (MACE Composite 1) | Baseline to Month 21 | This was 1 of 2 MACE composite endpoints and was a secondary efficacy endpoint. |
| Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for Cardiovascular Death, Nonfatal MI, or Nonfatal Stroke (MACE Composite 2) | Baseline to Month 21 | This was 1 of 2 MACE composite endpoints and was a secondary efficacy endpoint. |
| Number of Other Cardiovascular Events | Baseline to Month 21 | This was one of the secondary endpoints of the study. |
| Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Baseline to Month 18 | It was measured as ratio to baseline as percentage change based on log-transformed data : 100 x (exp(Mean change on log scale) - 1)It was measured as ratio to baseline as percentage change based on log-transformed data : 100 x (exp(Mean change on log scale) - 1). Ratio to baseline as %change mean (%) was used as the estimation parameter for both groups. |
| Model Adjusted Change From Baseline in Atheroma Volume to Month 18 | Baseline to Month 18 | IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication. |
Countries
Argentina, Brazil, Canada, Czechia, France, Germany, Greece, Hong Kong, India, Italy, Latvia, Mexico, Netherlands, Poland, Russia, South Korea, Spain, Sweden, Thailand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glipizide (GLP) 5 mg Glipizide (GLP) 5 mg once daily for 18 months | 337 |
| Rosiglitazone (RSG) 4 mg Rosiglitazone (RSG) 4 mg once daily for 18 months | 331 |
| Total | 668 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 16 |
| Overall Study | Baseline IVUS determined unevaluable | 12 | 11 |
| Overall Study | Hypoglycaemic events | 1 | 0 |
| Overall Study | Insufficient therapeutic effect | 0 | 1 |
| Overall Study | Lost to Follow-up | 8 | 6 |
| Overall Study | Low haemoglobin on screening | 1 | 0 |
| Overall Study | Missing data for participant | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 6 |
| Overall Study | Withdrawal by Subject | 32 | 32 |
| Overall Study | Withdrawn investigational product | 1 | 0 |
Baseline characteristics
| Characteristic | Glipizide (GLP) 5 mg | Rosiglitazone (RSG) 4 mg | Total |
|---|---|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 9.05 | 61.8 years STANDARD_DEVIATION 8.38 | 61.0 years STANDARD_DEVIATION 8.76 |
| Body Mass Index (BMI) | 29 kilograms per square meter (kg/m2) | 28 kilograms per square meter (kg/m2) | 29 kilograms per square meter (kg/m2) |
| Duration of cardiovascular disease | 0.79 Years | 0.59 Years | 0.73 Years |
| Duration of diabetes | 4.62 Years | 4.96 Years | 4.74 Years |
| Pre-study Treatment Diet and exercise regimen only | 64 Participants | 56 Participants | 120 Participants |
| Pre-study Treatment Oral anti-diabetic dual therapy | 90 Participants | 93 Participants | 183 Participants |
| Pre-study Treatment Oral anti-diabetic monotherapy | 183 Participants | 182 Participants | 365 Participants |
| Race/Ethnicity, Customized American Indian/Alaska native | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 7 Participants | 4 Participants | 11 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Mixed race | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Oriental | 70 Participants | 82 Participants | 152 Participants |
| Race/Ethnicity, Customized White | 255 Participants | 240 Participants | 495 Participants |
| Sex: Female, Male Female | 116 Participants | 98 Participants | 214 Participants |
| Sex: Female, Male Male | 221 Participants | 233 Participants | 454 Participants |
| Smoking history Current smoker | 57 Participants | 55 Participants | 112 Participants |
| Smoking history Former smoker | 128 Participants | 124 Participants | 252 Participants |
| Smoking history Missing | 0 Participants | 1 Participants | 1 Participants |
| Smoking history Never smoked | 152 Participants | 151 Participants | 303 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 117 / 337 | 98 / 331 |
| serious Total, serious adverse events | 71 / 337 | 71 / 331 |
Outcome results
Primary
Change From Baseline in Percent Atheroma Volume (PAV) to Month 18
The primary efficacy endpoint was change in PAV (defined as total atheroma volume divided by total vessel volume x 100) within a 40 mm segment in non-intervened coronary arteries from Baseline to Month 18, based upon Intravascular Ultrasound (IVUS) assessment.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population (Defined as all randomized participants who received at least one dose of study medication, with an evaluable Baseline and exit \[≥ 9 months\] IVUS imaging assessment.)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Change From Baseline in Percent Atheroma Volume (PAV) to Month 18 | Baseline | 40.593 percent (absolute change) | Standard Deviation 10.9717 |
| Glipizide (GLP) 5 mg | Change From Baseline in Percent Atheroma Volume (PAV) to Month 18 | Month 18 | 41.013 percent (absolute change) | Standard Deviation 11.1572 |
| Glipizide (GLP) 5 mg | Change From Baseline in Percent Atheroma Volume (PAV) to Month 18 | Change from Baseline | 0.420 percent (absolute change) | Standard Deviation 4.8085 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Percent Atheroma Volume (PAV) to Month 18 | Baseline | 40.422 percent (absolute change) | Standard Deviation 11.7506 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Percent Atheroma Volume (PAV) to Month 18 | Month 18 | 40.182 percent (absolute change) | Standard Deviation 11.4257 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Percent Atheroma Volume (PAV) to Month 18 | Change from Baseline | -0.240 percent (absolute change) | Standard Deviation 4.2421 |
Primary
Model Adjusted Change From Baseline in Percent Atheroma Volume (PAV) to Month 18
Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior Oral Anti-Hyperglycemic Diabetic Medications(s) (OAD).
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population (Defined as all randomized participants who received at least one dose of study medication, with an evaluable Baseline and exit \[≥ 9 months\] IVUS imaging assessment.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change From Baseline in Percent Atheroma Volume (PAV) to Month 18 | 0.43 percent (absolute change) | Standard Error 0.331 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change From Baseline in Percent Atheroma Volume (PAV) to Month 18 | -0.21 percent (absolute change) | Standard Error 0.331 |
p-value: 0.122195% CI: [-1.457, 0.173]ANCOVA
Secondary
Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18
IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Atheroma Area, Month 18 | 5.928 millimeters squared (mm2) | Standard Deviation 2.9615 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Change from Baseline in Vessel Area | -0.102 millimeters squared (mm2) | Standard Deviation 1.1954 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Vessel Area, Baseline | 14.364 millimeters squared (mm2) | Standard Deviation 5.1946 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Lumen Area, Baseline | 8.447 millimeters squared (mm2) | Standard Deviation 3.2037 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Change from Baseline in Atheroma Area | 0.010 millimeters squared (mm2) | Standard Deviation 0.6448 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Lumen Area, Month 18 | 8.335 millimeters squared (mm2) | Standard Deviation 3.2056 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Vessel Area, Month 18 | 14.261 millimeters squared (mm2) | Standard Deviation 5.1699 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Change from Baseline in Lumen Area | -0.113 millimeters squared (mm2) | Standard Deviation 1.2166 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Atheroma Area, Baseline | 5.918 millimeters squared (mm2) | Standard Deviation 2.9281 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Change from Baseline in Lumen Area | -0.075 millimeters squared (mm2) | Standard Deviation 0.9207 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Atheroma Area, Baseline | 5.748 millimeters squared (mm2) | Standard Deviation 2.5585 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Atheroma Area, Month 18 | 5.634 millimeters squared (mm2) | Standard Deviation 2.5594 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Change from Baseline in Atheroma Area | -0.114 millimeters squared (mm2) | Standard Deviation 0.699 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Vessel Area, Baseline | 14.166 millimeters squared (mm2) | Standard Deviation 4.8231 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Vessel Area, Month 18 | 13.977 millimeters squared (mm2) | Standard Deviation 4.8595 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Change from Baseline in Vessel Area | -0.189 millimeters squared (mm2) | Standard Deviation 0.9918 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Lumen Area, Baseline | 8.419 millimeters squared (mm2) | Standard Deviation 3.2847 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18 | Lumen Area, Month 18 | 8.344 millimeters squared (mm2) | Standard Deviation 3.3077 |
Secondary
Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18
IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Atheroma Volume, Month 18 | 249.625 millimeters cubed (mm3) | Standard Deviation 149.7098 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Change from Baseline in Vessel Volume | -6.290 millimeters cubed (mm3) | Standard Deviation 52.7032 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Vessel Volume, Baseline | 609.378 millimeters cubed (mm3) | Standard Deviation 311.7587 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Lumen Volume, Baseline | 359.726 millimeters cubed (mm3) | Standard Deviation 195.681 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Change from Baseline in Atheroma Volume | -0.123 millimeters cubed (mm3) | Standard Deviation 28.1627 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Lumen Volume, Month 18 | 353.513 millimeters cubed (mm3) | Standard Deviation 192.2419 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Vessel Volume, Month 18 | 603.088 millimeters cubed (mm3) | Standard Deviation 304.3434 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Change from Baseline in Lumen Volume | -6.213 millimeters cubed (mm3) | Standard Deviation 56.0042 |
| Glipizide (GLP) 5 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Atheroma Volume, Baseline | 249.747 millimeters cubed (mm3) | Standard Deviation 150.4095 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Change from Baseline in Lumen Volume | -4.012 millimeters cubed (mm3) | Standard Deviation 38.526 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Atheroma Volume, Baseline | 222.431 millimeters cubed (mm3) | Standard Deviation 137.4193 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Atheroma Volume, Month 18 | 218.576 millimeters cubed (mm3) | Standard Deviation 134.3462 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Change from Baseline in Atheroma Volume | -3.854 millimeters cubed (mm3) | Standard Deviation 25.8846 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Vessel Volume, Baseline | 555.062 millimeters cubed (mm3) | Standard Deviation 297.9848 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Vessel Volume, Month 18 | 547.186 millimeters cubed (mm3) | Standard Deviation 298.21 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Change from Baseline in Vessel Volume | -7.876 millimeters cubed (mm3) | Standard Deviation 40.4948 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Lumen Volume, Baseline | 332.688 millimeters cubed (mm3) | Standard Deviation 192.385 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18 | Lumen Volume, Month 18 | 328.676 millimeters cubed (mm3) | Standard Deviation 191.9313 |
Secondary
Change From Baseline in Normalized Atheroma Volume
IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Normalized atheroma volume is defined as mean atheroma area x median segment length in cohort.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Change From Baseline in Normalized Atheroma Volume | Baseline | 232.772 millimeters cubed (mm3) | Standard Deviation 115.163 |
| Glipizide (GLP) 5 mg | Change From Baseline in Normalized Atheroma Volume | Month 18 | 233.153 millimeters cubed (mm3) | Standard Deviation 116.4765 |
| Glipizide (GLP) 5 mg | Change From Baseline in Normalized Atheroma Volume | Change from Baseline | 0.381 millimeters cubed (mm3) | Standard Deviation 25.36 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Normalized Atheroma Volume | Baseline | 226.075 millimeters cubed (mm3) | Standard Deviation 100.6261 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Normalized Atheroma Volume | Month 18 | 221.599 millimeters cubed (mm3) | Standard Deviation 100.6606 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline in Normalized Atheroma Volume | Change from Baseline | -4.476 millimeters cubed (mm3) | Standard Deviation 27.4901 |
Secondary
Change From Baseline to Month 18 in LDL-c/HDL-c Ratio
From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Change From Baseline to Month 18 in LDL-c/HDL-c Ratio | -0.365 ratio | Standard Error 0.061 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline to Month 18 in LDL-c/HDL-c Ratio | -0.226 ratio | Standard Error 0.0629 |
Secondary
Change From Baseline to Month 18 in LDL-c Peak Particle Density Measured by LDL Relative Flotation
From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Change From Baseline to Month 18 in LDL-c Peak Particle Density Measured by LDL Relative Flotation | 0.0040 Ratio | Standard Error 0.00158 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline to Month 18 in LDL-c Peak Particle Density Measured by LDL Relative Flotation | 0.0204 Ratio | Standard Error 0.00163 |
Secondary
Change From Baseline to Month 18 in Total Cholesterol/HDL-c Ratio
From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Change From Baseline to Month 18 in Total Cholesterol/HDL-c Ratio | -0.495 ratio | Standard Error 0.0838 |
| Rosiglitazone (RSG) 4 mg | Change From Baseline to Month 18 in Total Cholesterol/HDL-c Ratio | -0.377 ratio | Standard Error 0.0862 |
Secondary
Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline
IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population with last observation carried forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Month 18 | 7.185 millimeters squared (mm2) | Standard Deviation 3.2957 |
| Glipizide (GLP) 5 mg | Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Baseline | 7.569 millimeters squared (mm2) | Standard Deviation 3.2718 |
| Glipizide (GLP) 5 mg | Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Change from Baseline | -0.384 millimeters squared (mm2) | Standard Deviation 1.0608 |
| Rosiglitazone (RSG) 4 mg | Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Baseline | 7.093 millimeters squared (mm2) | Standard Deviation 3.0042 |
| Rosiglitazone (RSG) 4 mg | Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Month 18 | 6.625 millimeters squared (mm2) | Standard Deviation 3.0741 |
| Rosiglitazone (RSG) 4 mg | Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Change from Baseline | -0.468 millimeters squared (mm2) | Standard Deviation 1.137 |
Secondary
Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline
IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population with last observation carried forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Baseline | 75.649 millimeters cubed (mm3) | Standard Deviation 32.6125 |
| Glipizide (GLP) 5 mg | Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Month 18 | 72.225 millimeters cubed (mm3) | Standard Deviation 33.2887 |
| Glipizide (GLP) 5 mg | Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Change from Baseline | -3.424 millimeters cubed (mm3) | Standard Deviation 11.9263 |
| Rosiglitazone (RSG) 4 mg | Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Baseline | 70.961 millimeters cubed (mm3) | Standard Deviation 29.961 |
| Rosiglitazone (RSG) 4 mg | Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Month 18 | 66.020 millimeters cubed (mm3) | Standard Deviation 30.7228 |
| Rosiglitazone (RSG) 4 mg | Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | Change from Baseline | -4.941 millimeters cubed (mm3) | Standard Deviation 12.2005 |
Secondary
Model Adjusted Change From Baseline in Atheroma Area to Month 18
IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change From Baseline in Atheroma Area to Month 18 | 0.03 millimeters square (mm2) | Standard Error 0.05 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change From Baseline in Atheroma Area to Month 18 | -0.10 millimeters square (mm2) | Standard Error 0.05 |
Secondary
Model Adjusted Change From Baseline in Atheroma Volume to Month 18
IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change From Baseline in Atheroma Volume to Month 18 | 0.98 millimeters cubed (mm3) | Standard Error 2.001 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change From Baseline in Atheroma Volume to Month 18 | -3.60 millimeters cubed (mm3) | Standard Error 2.002 |
Secondary
Model Adjusted Change From Baseline in Lumen Area to Month 18
IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change From Baseline in Lumen Area to Month 18 | -0.14 millimeters square (mm2) | Standard Error 0.079 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change From Baseline in Lumen Area to Month 18 | -0.11 millimeters square (mm2) | Standard Error 0.079 |
Secondary
Model Adjusted Change From Baseline in Lumen Volume to Month 18
IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change From Baseline in Lumen Volume to Month 18 | -4.91 millimeters cubed (mm3) | Standard Error 3.545 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change From Baseline in Lumen Volume to Month 18 | -4.59 millimeters cubed (mm3) | Standard Error 3.526 |
Secondary
Model Adjusted Change From Baseline in Normalized Atheroma Volume
IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Normalized atheroma volume is defined as mean atheroma area x median segment length in cohort. Model Adjusted Change = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change From Baseline in Normalized Atheroma Volume | 1.20 millimeters cubed (mm3) | Standard Error 1.974 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change From Baseline in Normalized Atheroma Volume | -3.92 millimeters cubed (mm3) | Standard Error 1.983 |
Secondary
Model Adjusted Change From Baseline in Vessel Area to Month 18
IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change From Baseline in Vessel Area to Month 18 | -0.10 millimeters square (mm2) | Standard Error 0.082 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change From Baseline in Vessel Area to Month 18 | -0.21 millimeters square (mm2) | Standard Error 0.082 |
Secondary
Model Adjusted Change From Baseline in Vessel Volume to Month 18
IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change From Baseline in Vessel Volume to Month 18 | -4.56 millimeters cubed (mm3) | Standard Error 3.479 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change From Baseline in Vessel Volume to Month 18 | -8.13 millimeters cubed (mm3) | Standard Error 3.466 |
Secondary
Model Adjusted Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline
IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area. Model Adjusted Change = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population with last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | -0.39 millimeters squared (mm2) | Standard Error 0.081 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | -0.50 millimeters squared (mm2) | Standard Error 0.082 |
Secondary
Model Adjusted Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline
IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area. Model Adjusted Change = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.
Time frame: Baseline to Month 18
Population: IVUS Evaluable Population with last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | -3.56 millimeters cubed (mm3) | Standard Error 0.892 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline | -5.28 millimeters cubed (mm3) | Standard Error 0.898 |
Secondary
Model Adjusted Change in Fasting Plasma Glucose (FPG) From Baseline to Month 18
From repeated measures analysis model: Change = Baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change in Fasting Plasma Glucose (FPG) From Baseline to Month 18 | -0.46 millimole/Liter (mmol/L) | Standard Error 0.138 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change in Fasting Plasma Glucose (FPG) From Baseline to Month 18 | -1.34 millimole/Liter (mmol/L) | Standard Error 0.145 |
Secondary
Model Adjusted Change in Glycated Hemoglobin (HbA1c) From Baseline to Month 18
From repeated measures analysis model: Change = Baseline + visit + sex + region + treatment + prior Oral Anti-Hyperglycemic Diabetic Medications(s) (OAD) + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: Intent-to-Treat (ITT) Population without Last Observation Carried Forward (LOCF). ITT population was defined as all participants in the study who were randomized and have at least one on-therapy value for an efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Change in Glycated Hemoglobin (HbA1c) From Baseline to Month 18 | -0.20 Percentage | Standard Error 0.051 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Change in Glycated Hemoglobin (HbA1c) From Baseline to Month 18 | -0.30 Percentage | Standard Error 0.053 |
Secondary
Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18
It was measured as ratio to baseline as percentage change based on log-transformed data : 100 x (exp(Mean change on log scale) - 1). Model Adjusted change based on ANCOVA: Log(value) - log(Baseline) = log(Baseline) + sex + region + treatment + prior OAD + cardiac procedure.
Time frame: Baseline to Month 18
Population: ITT Population with LOCF
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Adjusted Geometric Mean + Standard Error | -4.865 percent change | -17.465 |
| Glipizide (GLP) 5 mg | Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Adjusted Geometric Mean | -11.388 percent change | — |
| Glipizide (GLP) 5 mg | Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Adjusted Geometric Mean - Standard Error | -17.465 percent change | — |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Adjusted Geometric Mean + Standard Error | 24.576 percent change | 7.499 |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Adjusted Geometric Mean | 15.720 percent change | — |
| Rosiglitazone (RSG) 4 mg | Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Adjusted Geometric Mean - Standard Error | 7.499 percent change | — |
Secondary
Number of Other Cardiovascular Events
This was one of the secondary endpoints of the study.
Time frame: Baseline to Month 21
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Number of Other Cardiovascular Events | Non-MACE congestive heart failure | 3 Number of events |
| Glipizide (GLP) 5 mg | Number of Other Cardiovascular Events | Non-fatal stroke | 1 Number of events |
| Glipizide (GLP) 5 mg | Number of Other Cardiovascular Events | Cardiovascular death | 3 Number of events |
| Glipizide (GLP) 5 mg | Number of Other Cardiovascular Events | Coronary revascularization | 27 Number of events |
| Glipizide (GLP) 5 mg | Number of Other Cardiovascular Events | All-cause death | 7 Number of events |
| Glipizide (GLP) 5 mg | Number of Other Cardiovascular Events | Hospitalization for recurrent myocardial ischemia | 7 Number of events |
| Glipizide (GLP) 5 mg | Number of Other Cardiovascular Events | Non-fatal myocardial infarction | 6 Number of events |
| Rosiglitazone (RSG) 4 mg | Number of Other Cardiovascular Events | Non-MACE congestive heart failure | 8 Number of events |
| Rosiglitazone (RSG) 4 mg | Number of Other Cardiovascular Events | All-cause death | 8 Number of events |
| Rosiglitazone (RSG) 4 mg | Number of Other Cardiovascular Events | Cardiovascular death | 4 Number of events |
| Rosiglitazone (RSG) 4 mg | Number of Other Cardiovascular Events | Non-fatal myocardial infarction | 7 Number of events |
| Rosiglitazone (RSG) 4 mg | Number of Other Cardiovascular Events | Non-fatal stroke | 5 Number of events |
| Rosiglitazone (RSG) 4 mg | Number of Other Cardiovascular Events | Coronary revascularization | 26 Number of events |
| Rosiglitazone (RSG) 4 mg | Number of Other Cardiovascular Events | Hospitalization for recurrent myocardial ischemia | 11 Number of events |
Secondary
Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for All-cause Death, Non-fatal MI, Non-fatal Stroke, Coronary Revascularization, or Hospitalization for Recurrent Myocardial Ischemia (MACE Composite 1)
This was 1 of 2 MACE composite endpoints and was a secondary efficacy endpoint.
Time frame: Baseline to Month 21
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glipizide (GLP) 5 mg | Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for All-cause Death, Non-fatal MI, Non-fatal Stroke, Coronary Revascularization, or Hospitalization for Recurrent Myocardial Ischemia (MACE Composite 1) | 38 Participants |
| Rosiglitazone (RSG) 4 mg | Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for All-cause Death, Non-fatal MI, Non-fatal Stroke, Coronary Revascularization, or Hospitalization for Recurrent Myocardial Ischemia (MACE Composite 1) | 39 Participants |
Secondary
Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for Cardiovascular Death, Nonfatal MI, or Nonfatal Stroke (MACE Composite 2)
This was 1 of 2 MACE composite endpoints and was a secondary efficacy endpoint.
Time frame: Baseline to Month 21
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glipizide (GLP) 5 mg | Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for Cardiovascular Death, Nonfatal MI, or Nonfatal Stroke (MACE Composite 2) | 10 Participants |
| Rosiglitazone (RSG) 4 mg | Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for Cardiovascular Death, Nonfatal MI, or Nonfatal Stroke (MACE Composite 2) | 14 Participants |
Secondary
Percent Change From Baseline to Month 18 in Apoprotein B (apoB)
Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Apoprotein B (apoB) | Adjusted Geometric Mean + Standard Error | -6.588 percent change | -10.021 |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Apoprotein B (apoB) | Adjusted Geometric Mean | -8.320 percent change | — |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Apoprotein B (apoB) | Adjusted Geometric Mean - Standard Error | -10.021 percent change | — |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Apoprotein B (apoB) | Adjusted Geometric Mean + Standard Error | -6.967 percent change | -10.488 |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Apoprotein B (apoB) | Adjusted Geometric Mean | -8.744 percent change | — |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Apoprotein B (apoB) | Adjusted Geometric Mean - Standard Error | -10.488 percent change | — |
Secondary
Percent Change From Baseline to Month 18 in Free Fatty Acids (FFA)
Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Free Fatty Acids (FFA) | Adjusted Geometric Mean + Standard Error | 32.909 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Free Fatty Acids (FFA) | Adjusted Geometric Mean | 27.303 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Free Fatty Acids (FFA) | Adjusted Geometric Mean - Standard Error | 21.943 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Free Fatty Acids (FFA) | Adjusted Geometric Mean + Standard Error | 13.835 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Free Fatty Acids (FFA) | Adjusted Geometric Mean | 8.880 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Free Fatty Acids (FFA) | Adjusted Geometric Mean - Standard Error | 4.142 percent change |
Secondary
Percent Change From Baseline to Month 18 in HDL-2
Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in HDL-2 | Adjusted Geometric Mean + Standard Error | 2.065 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in HDL-2 | Adjusted Geometric Mean | -0.783 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in HDL-2 | Adjusted Geometric Mean - Standard Error | -3.550 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in HDL-2 | Adjusted Geometric Mean + Standard Error | 18.241 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in HDL-2 | Adjusted Geometric Mean | 14.821 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in HDL-2 | Adjusted Geometric Mean - Standard Error | 11.507 percent change |
Secondary
Percent Change From Baseline to Month 18 in HDL-3
Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in HDL-3 | Adjusted Geometric Mean + Standard Error | 10.683 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in HDL-3 | Adjusted Geometric Mean | 9.074 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in HDL-3 | Adjusted Geometric Mean - Standard Error | 7.490 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in HDL-3 | Adjusted Geometric Mean + Standard Error | 15.165 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in HDL-3 | Adjusted Geometric Mean | 13.440 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in HDL-3 | Adjusted Geometric Mean - Standard Error | 11.732 percent change |
Secondary
Percent Change From Baseline to Month 18 in High Density Lipoprotein Cholesterol (HDL-c)
Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in High Density Lipoprotein Cholesterol (HDL-c) | Adjusted Geometric Mean + Standard Error | 7.208 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in High Density Lipoprotein Cholesterol (HDL-c) | Adjusted Geometric Mean | 5.710 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in High Density Lipoprotein Cholesterol (HDL-c) | Adjusted Geometric Mean - Standard Error | 4.233 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in High Density Lipoprotein Cholesterol (HDL-c) | Adjusted Geometric Mean + Standard Error | 15.104 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in High Density Lipoprotein Cholesterol (HDL-c) | Adjusted Geometric Mean | 13.440 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in High Density Lipoprotein Cholesterol (HDL-c) | Adjusted Geometric Mean - Standard Error | 11.808 percent change |
Secondary
Percent Change From Baseline to Month 18 in Low Density Lipoprotein Cholesterol (LDL-c)
Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Low Density Lipoprotein Cholesterol (LDL-c) | Adjusted Geometric Mean + Standard Error | -8.955 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Low Density Lipoprotein Cholesterol (LDL-c) | Adjusted Geometric Mean | -11.600 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Low Density Lipoprotein Cholesterol (LDL-c) | Adjusted Geometric Mean - Standard Error | -14.172 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Low Density Lipoprotein Cholesterol (LDL-c) | Adjusted Geometric Mean + Standard Error | 1.795 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Low Density Lipoprotein Cholesterol (LDL-c) | Adjusted Geometric Mean | -1.237 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Low Density Lipoprotein Cholesterol (LDL-c) | Adjusted Geometric Mean - Standard Error | -4.180 percent change |
Secondary
Percent Change From Baseline to Month 18 in Total Cholesterol (TC)
Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Total Cholesterol (TC) | Adjusted Geometric Mean + Standard Error | -4.205 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Total Cholesterol (TC) | Adjusted Geometric Mean | -5.644 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Total Cholesterol (TC) | Adjusted Geometric Mean - Standard Error | -7.062 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Total Cholesterol (TC) | Adjusted Geometric Mean + Standard Error | 3.151 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Total Cholesterol (TC) | Adjusted Geometric Mean | 1.567 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Total Cholesterol (TC) | Adjusted Geometric Mean - Standard Error | 0.007 percent change |
Secondary
Percent Change From Baseline to Month 18 in Triglycerides (TG)
Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Triglycerides (TG) | Adjusted Geometric Mean + Standard Error | -7.415 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Triglycerides (TG) | Adjusted Geometric Mean | -10.309 percent change |
| Glipizide (GLP) 5 mg | Percent Change From Baseline to Month 18 in Triglycerides (TG) | Adjusted Geometric Mean - Standard Error | -13.110 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Triglycerides (TG) | Adjusted Geometric Mean + Standard Error | -13.601 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Triglycerides (TG) | Adjusted Geometric Mean | -16.381 percent change |
| Rosiglitazone (RSG) 4 mg | Percent Change From Baseline to Month 18 in Triglycerides (TG) | Adjusted Geometric Mean - Standard Error | -19.067 percent change |
Secondary
Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18
It was measured as ratio to baseline as percentage change based on log-transformed data : 100 x (exp(Mean change on log scale) - 1)It was measured as ratio to baseline as percentage change based on log-transformed data : 100 x (exp(Mean change on log scale) - 1). Ratio to baseline as %change mean (%) was used as the estimation parameter for both groups.
Time frame: Baseline to Month 18
Population: ITT Population with LOCF
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Mean + Standard Error | 1.141 percent change | -13.764 |
| Glipizide (GLP) 5 mg | Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Mean | -6.608 percent change | — |
| Glipizide (GLP) 5 mg | Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Mean - Standard Error | -13.764 percent change | — |
| Rosiglitazone (RSG) 4 mg | Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Mean + Standard Error | 30.189 percent change | 11.683 |
| Rosiglitazone (RSG) 4 mg | Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Mean | 20.582 percent change | — |
| Rosiglitazone (RSG) 4 mg | Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18 | Mean - Standard Error | 11.683 percent change | — |
Secondary
Repeated Measures Analysis of Percent Change in hsCRP From Baseline to Month 18
Changes in cardiovascular biomarkers from Baseline to Month 18, such as high sensitivity C-reactive protein (hsCRP) . Repeated measures analysis model: Log(value) - log(baseline) = log(baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Repeated Measures Analysis of Percent Change in hsCRP From Baseline to Month 18 | Adjusted Geometric Mean + Standard Error | -62.82 percent change | -67.4 |
| Glipizide (GLP) 5 mg | Repeated Measures Analysis of Percent Change in hsCRP From Baseline to Month 18 | Adjusted Geometric Mean | -65.18 percent change | — |
| Glipizide (GLP) 5 mg | Repeated Measures Analysis of Percent Change in hsCRP From Baseline to Month 18 | Adjusted Geometric Mean - Standard Error | -67.40 percent change | — |
| Rosiglitazone (RSG) 4 mg | Repeated Measures Analysis of Percent Change in hsCRP From Baseline to Month 18 | Adjusted Geometric Mean + Standard Error | -80.33 percent change | -82.84 |
| Rosiglitazone (RSG) 4 mg | Repeated Measures Analysis of Percent Change in hsCRP From Baseline to Month 18 | Adjusted Geometric Mean | -81.63 percent change | — |
| Rosiglitazone (RSG) 4 mg | Repeated Measures Analysis of Percent Change in hsCRP From Baseline to Month 18 | Adjusted Geometric Mean - Standard Error | -82.84 percent change | — |
Secondary
Repeated Measures Analysis of Percent Change in MMP 9 From Baseline to Month 18
Changes in cardiovascular biomarkers from Baseline to Month 18, such as matrix metalloproteinase-9 (MMP-9). Repeated measures analysis model: Log(value) - log(baseline) = log(baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time frame: Baseline to Month 18
Population: ITT Population without LOCF
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Glipizide (GLP) 5 mg | Repeated Measures Analysis of Percent Change in MMP 9 From Baseline to Month 18 | Adjusted Geometric Mean + Standard Error | -26.5 percent change | -34.3 |
| Glipizide (GLP) 5 mg | Repeated Measures Analysis of Percent Change in MMP 9 From Baseline to Month 18 | Adjusted Geometric Mean | -30.5 percent change | — |
| Glipizide (GLP) 5 mg | Repeated Measures Analysis of Percent Change in MMP 9 From Baseline to Month 18 | Adjusted Geometric Mean - Standard Error | -34.3 percent change | — |
| Rosiglitazone (RSG) 4 mg | Repeated Measures Analysis of Percent Change in MMP 9 From Baseline to Month 18 | Adjusted Geometric Mean + Standard Error | -38.8 percent change | -45.5 |
| Rosiglitazone (RSG) 4 mg | Repeated Measures Analysis of Percent Change in MMP 9 From Baseline to Month 18 | Adjusted Geometric Mean | -42.2 percent change | — |
| Rosiglitazone (RSG) 4 mg | Repeated Measures Analysis of Percent Change in MMP 9 From Baseline to Month 18 | Adjusted Geometric Mean - Standard Error | -45.5 percent change | — |