Rosiglitazone Versus a Sulfonylurea On Progression Of Atherosclerosis In Patients With Heart Disease And Type 2 Diabetes

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00116831
• Collaborator: (none)
• Enrollment: 672
• Locations: 156
• Arms: 2
• Duration (Months): 43
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: Glipizide; Drug: rosiglitazone maleate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 672 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, 18 Month, Multicenter, Randomized, Double-Blind, Active-Controlled Clinical Trial to Compare Rosiglitazone Versus Glipizide on the Progression of Atherosclerosis in Subjects With Type 2 Diabetes Mellitus and Cardiovascular Disease (APPROACH)
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Glipizide oral anti-diabetic medication	Drug: Glipizide; oral anti-diabetic medication
Experimental: rosiglitazone maleate oral anti-diabetic medication	Drug: rosiglitazone maleate; oral antidiabetic medication

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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

2. 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.

3. 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.

4. 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.

5. 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

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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

12. 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.

13. 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

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. Number of Other Cardiovascular Events [Baseline to Month 21]

    This was one of the secondary endpoints of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35235
2	GSK Investigational Site	Scottsdale	Arizona	United States	85251
3	GSK Investigational Site	Tucson	Arizona	United States	85745
4	GSK Investigational Site	Burbank	California	United States	91505
5	GSK Investigational Site	Huntington Beach	California	United States	92648
6	GSK Investigational Site	Los Angeles	California	United States	90017
7	GSK Investigational Site	Mission Viejo	California	United States	92691
8	GSK Investigational Site	Sacramento	California	United States	95817
9	GSK Investigational Site	Sacramento	California	United States	95825
10	GSK Investigational Site	Torrance	California	United States	90503
11	GSK Investigational Site	Torrance	California	United States	90509
12	GSK Investigational Site	Denver	Colorado	United States	80220
13	GSK Investigational Site	Englewood	Colorado	United States	80113
14	GSK Investigational Site	Washington	District of Columbia	United States	20010
15	GSK Investigational Site	Melbourne	Florida	United States	32901
16	GSK Investigational Site	Tampa	Florida	United States	33609
17	GSK Investigational Site	Atlanta	Georgia	United States	30309
18	GSK Investigational Site	Peoria	Illinois	United States	61615
19	GSK Investigational Site	Springfield	Illinois	United States	62702
20	GSK Investigational Site	Indianapolis	Indiana	United States	46260
21	GSK Investigational Site	Baltimore	Maryland	United States	21287
22	GSK Investigational Site	Columbia	Maryland	United States	21044
23	GSK Investigational Site	Springfield	Massachusetts	United States	01199
24	GSK Investigational Site	Springfield	Missouri	United States	65807
25	GSK Investigational Site	New Brunswick	New Jersey	United States	08903
26	GSK Investigational Site	Albany	New York	United States	12208
27	GSK Investigational Site	New York	New York	United States	10032
28	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
29	GSK Investigational Site	Winston-Salem	North Carolina	United States	27157
30	GSK Investigational Site	Canton	Ohio	United States	44708
31	GSK Investigational Site	Beaver	Pennsylvania	United States	15009
32	GSK Investigational Site	Camp Hill	Pennsylvania	United States	17011
33	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19141
34	GSK Investigational Site	Jackson	Tennessee	United States	38301
35	GSK Investigational Site	Corpus Christi	Texas	United States	78404
36	GSK Investigational Site	San Antonio	Texas	United States	78207
37	GSK Investigational Site	San Antonio	Texas	United States	78229
38	GSK Investigational Site	Bellevue	Washington	United States	98004
39	GSK Investigational Site	Milwaukee	Wisconsin	United States	53215
40	GSK Investigational Site	Capital Federal	Buenos Aires	Argentina	1181
41	GSK Investigational Site	Capital Federal	Buenos Aires	Argentina	C1155ADP
42	GSK Investigational Site	Capital Federal	Buenos Aires	Argentina	C1437JCP
43	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	B1704ETD
44	GSK Investigational Site	Munro	Buenos Aires	Argentina	1605
45	GSK Investigational Site	San Justo	Buenos Aires	Argentina	B7118XAB
46	GSK Investigational Site	San Martín	Buenos Aires	Argentina	1650
47	GSK Investigational Site	Córdoba	Córdova	Argentina	5000
48	GSK Investigational Site	Buenos Aires		Argentina	1428
49	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	1221
50	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	1405
51	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	1416
52	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	C1416DRW
53	GSK Investigational Site	Cordoba		Argentina	5000
54	GSK Investigational Site	Moron-Provincia de Buenos Aires		Argentina	1709
55	GSK Investigational Site	Ribeirão Preto	São Paulo	Brazil	14048-900
56	GSK Investigational Site	São Paulo		Brazil	04012-909
57	GSK Investigational Site	São Paulo		Brazil	05403-000
58	GSK Investigational Site	São Paulo		Brazil	05651-901
59	GSK Investigational Site	Hamilton	Ontario	Canada	L8L 2X2
60	GSK Investigational Site	London	Ontario	Canada	N6A 4V2
61	GSK Investigational Site	Toronto	Ontario	Canada	M4N 3M5
62	GSK Investigational Site	Toronto	Ontario	Canada	M5B 1W8
63	GSK Investigational Site	Montreal	Quebec	Canada	H1T 1C8
64	GSK Investigational Site	Hradec Kralove		Czech Republic	500 05
65	GSK Investigational Site	Corbeil Essonnes Cedex		France	91106
66	GSK Investigational Site	Le Plessis Robinson		France	92350
67	GSK Investigational Site	Marseille		France	13005
68	GSK Investigational Site	Rennes Cedex		France	35033
69	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg	Germany	69120
70	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg	Germany	69126
71	GSK Investigational Site	Mannheim	Baden-Wuerttemberg	Germany	68161
72	GSK Investigational Site	Coburg	Bayern	Germany	96450
73	GSK Investigational Site	Kronach	Bayern	Germany	96317
74	GSK Investigational Site	Kulmbach	Bayern	Germany	95326
75	GSK Investigational Site	Lichtenfels	Bayern	Germany	96215
76	GSK Investigational Site	Hirschhorn	Hessen	Germany	69434
77	GSK Investigational Site	Lampertheim	Hessen	Germany	68623
78	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44789
79	GSK Investigational Site	Dinslaken	Nordrhein-Westfalen	Germany	46537
80	GSK Investigational Site	Dormagen	Nordrhein-Westfalen	Germany	41539
81	GSK Investigational Site	Dortmund	Nordrhein-Westfalen	Germany	44137
82	GSK Investigational Site	Dortmund	Nordrhein-Westfalen	Germany	44328
83	GSK Investigational Site	Dortmund	Nordrhein-Westfalen	Germany	44339
84	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen	Germany	40454
85	GSK Investigational Site	Duisburg	Nordrhein-Westfalen	Germany	47119
86	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45122
87	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45136
88	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45309
89	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45329
90	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45355
91	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45359
92	GSK Investigational Site	Gelsenkirchen	Nordrhein-Westfalen	Germany	45881
93	GSK Investigational Site	Herne	Nordrhein-Westfalen	Germany	44623
94	GSK Investigational Site	Herne	Nordrhein-Westfalen	Germany	44653
95	GSK Investigational Site	Leverkusen	Nordrhein-Westfalen	Germany	51377
96	GSK Investigational Site	Luenen	Nordrhein-Westfalen	Germany	44534
97	GSK Investigational Site	Marl	Nordrhein-Westfalen	Germany	45772
98	GSK Investigational Site	Oberhausen	Nordrhein-Westfalen	Germany	46049
99	GSK Investigational Site	Ludwigshafen	Rheinland-Pfalz	Germany	67063
100	GSK Investigational Site	Rhaunen	Rheinland-Pfalz	Germany	55624
101	GSK Investigational Site	Speyer	Rheinland-Pfalz	Germany	67346
102	GSK Investigational Site	Trier	Rheinland-Pfalz	Germany	54292
103	GSK Investigational Site	Trier	Rheinland-Pfalz	Germany	54296
104	GSK Investigational Site	Friedrichsthal	Saarland	Germany	66299
105	GSK Investigational Site	Saarlouis	Saarland	Germany	66740
106	GSK Investigational Site	Sr. Ingbert	Saarland	Germany	66386
107	GSK Investigational Site	Athens		Greece	115 26
108	GSK Investigational Site	Athens		Greece	115 27
109	GSK Investigational Site	Athens		Greece	155 62
110	GSK Investigational Site	Athens		Greece	176 74
111	GSK Investigational Site	Causeway Bay		Hong Kong
112	GSK Investigational Site	Kowloon		Hong Kong
113	GSK Investigational Site	Kwun Tong		Hong Kong
114	GSK Investigational Site	Pokfulam		Hong Kong
115	GSK Investigational Site	Shatin		Hong Kong
116	GSK Investigational Site	Mumbai		India	400005
117	GSK Investigational Site	New Delhi		India	110017
118	GSK Investigational Site	Udine	Friuli-Venezia-Giulia	Italy	33100
119	GSK Investigational Site	Rozzano (Mi)	Lombardia	Italy	20089
120	GSK Investigational Site	Seoul		Korea, Republic of	110-744
121	GSK Investigational Site	Seoul		Korea, Republic of	120-752
122	GSK Investigational Site	Seoul		Korea, Republic of	138-736
123	GSK Investigational Site	Suwon-Si		Korea, Republic of	443-721
124	GSK Investigational Site	Riga		Latvia	LV1002
125	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44340
126	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64060
127	GSK Investigational Site	Breda		Netherlands	4818 CK
128	GSK Investigational Site	Eindhoven		Netherlands	5623 EJ
129	GSK Investigational Site	Enschede		Netherlands	7511JX
130	GSK Investigational Site	Nieuwegein		Netherlands	3435 CM
131	GSK Investigational Site	Rotterdam		Netherlands	3015 GD
132	GSK Investigational Site	Rotterdam		Netherlands	3075 EA
133	GSK Investigational Site	Zwolle		Netherlands	8011 JW
134	GSK Investigational Site	Bialystok		Poland	15-276
135	GSK Investigational Site	Kalisz		Poland	62-800
136	GSK Investigational Site	Katowice		Poland	40-635
137	GSK Investigational Site	Poznan		Poland	60-355
138	GSK Investigational Site	Warszawa		Poland	04-628
139	GSK Investigational Site	Moscow		Russian Federation	105 229
140	GSK Investigational Site	Moscow		Russian Federation	121552
141	GSK Investigational Site	Moscow		Russian Federation	123182
142	GSK Investigational Site	Alicante		Spain	03010
143	GSK Investigational Site	Badalona		Spain	08916
144	GSK Investigational Site	Barcelona		Spain	08035
145	GSK Investigational Site	Barcelona		Spain	08036
146	GSK Investigational Site	Barcelona		Spain	08097
147	GSK Investigational Site	Madrid		Spain	28035
148	GSK Investigational Site	Malaga		Spain	29010
149	GSK Investigational Site	Marid		Spain	28040
150	GSK Investigational Site	Murcia		Spain	30120
151	GSK Investigational Site	Oviedo		Spain	33006
152	GSK Investigational Site	San Juan/Alicante		Spain	03550
153	GSK Investigational Site	Göteborg		Sweden	SE-413 45
154	GSK Investigational Site	Stockholm		Sweden	SE-171 76
155	GSK Investigational Site	Bangkok		Thailand	10330
156	GSK Investigational Site	Chiang Mai		Thailand	50200

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• García-García HM, Garg S, Brugaletta S, Morocutti G, Ratner RE, Kolatkar NS, Kravitz BG, Miller DM, Huang C, Nesto RW, Serruys PW; APPROACH study group. Evaluation of in-stent restenosis in the APPROACH trial (Assessment on the Prevention of Progression by Rosiglitazone On Atherosclerosis in diabetes patients with Cardiovascular History). Int J Cardiovasc Imaging. 2012 Mar;28(3):455-65. doi: 10.1007/s10554-011-9836-z. Epub 2011 Feb 27.
• Gerstein HC, Ratner RE, Cannon CP, Serruys PW, García-García HM, van Es GA, Kolatkar NS, Kravitz BG, Miller DM, Huang C, Fitzgerald PJ, Nesto RW; APPROACH Study Group. Effect of rosiglitazone on progression of coronary atherosclerosis in patients with type 2 diabetes mellitus and coronary artery disease: the assessment on the prevention of progression by rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history trial. Circulation. 2010 Mar 16;121(10):1176-87. doi: 10.1161/CIRCULATIONAHA.109.881003. Epub 2010 Mar 1.
• Nesto RW. Effect of rosiglitazone versus glipizide on progression of coronary atherosclerosis in patients with type 2 diabetes and coronary artery disease. American Heart Association Scientific Sessions. November 12, 2008, New Orleans, LA. (http://directnews.americanheart.org/extras/pdfs/approach_slides.pdf)
• Ratner RE, Cannon CP, Gerstein HC, Nesto RW, Serruys PW, Van Es GA, Kolatkar NS, Kravitz BG, Zalewski A, Fitzgerald PJ; APPROACH Study Group. Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in diabetes patients with Cardiovascular History (APPROACH): study design and baseline characteristics. Am Heart J. 2008 Dec;156(6):1074-9. doi: 10.1016/j.ahj.2008.07.025. Epub 2008 Oct 11.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00116831
• Other Study ID Numbers: AVD100521
• First Posted: Jul 1, 2005
• Last Update Posted: Mar 23, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: atheroma; IVUS; Intravascular ultrasound; atherosclerosis
• Additional relevant MeSH terms: Atherosclerosis; Rosiglitazone; Glipizide

Study Results

Participant Flow

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Period Title: Overall Study
STARTED	337	331
COMPLETED	264	259
NOT COMPLETED	73	72

Baseline Characteristics

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg	Total
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months	Total of all reporting groups
Overall Participants	337	331	668
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (9.05)	61.8 (8.38)	61.0 (8.76)
Sex: Female, Male (Count of Participants)
Female	116 34.4%	98 29.6%	214 32%
Male	221 65.6%	233 70.4%	454 68%
Race/Ethnicity, Customized (Number) [Number]
White	255 75.7%	240 72.5%	495 74.1%
Oriental	70 20.8%	82 24.8%	152 22.8%
Black	7 2.1%	4 1.2%	11 1.6%
Mixed race	4 1.2%	2 0.6%	6 0.9%
Missing	0 0%	1 0.3%	1 0.1%
American Indian/Alaska native	1 0.3%	2 0.6%	3 0.4%
Pre-study Treatment (Number) [Number]
Diet and exercise regimen only	64 19%	56 16.9%	120 18%
Oral anti-diabetic monotherapy	183 54.3%	182 55%	365 54.6%
Oral anti-diabetic dual therapy	90 26.7%	93 28.1%	183 27.4%
Smoking history (Number) [Number]
Never smoked	152 45.1%	151 45.6%	303 45.4%
Current smoker	57 16.9%	55 16.6%	112 16.8%
Former smoker	128 38%	124 37.5%	252 37.7%
Missing	0 0%	1 0.3%	1 0.1%
Body Mass Index (BMI) (kilograms per square meter (kg/m2)) [Median (Full Range) ]
Median (Full Range) [kilograms per square meter (kg/m2)]	29	28	29
Duration of cardiovascular disease (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	0.79	0.59	0.73
Duration of diabetes (Years) [Median (Full Range) ]
Median (Full Range) [Years]	4.62	4.96	4.74

Outcome Measures

1. Secondary Outcome

Title	Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18
Description	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18
Time Frame	Baseline to Month 18

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Atheroma Volume, Baseline	249.747 (150.4095)	222.431 (137.4193)
Atheroma Volume, Month 18	249.625 (149.7098)	218.576 (134.3462)
Change from Baseline in Atheroma Volume	-0.123 (28.1627)	-3.854 (25.8846)
Vessel Volume, Baseline	609.378 (311.7587)	555.062 (297.9848)
Vessel Volume, Month 18	603.088 (304.3434)	547.186 (298.2100)
Change from Baseline in Vessel Volume	-6.290 (52.7032)	-7.876 (40.4948)
Lumen Volume, Baseline	359.726 (195.6810)	332.688 (192.3850)
Lumen Volume, Month 18	353.513 (192.2419)	328.676 (191.9313)
Change from Baseline in Lumen Volume	-6.213 (56.0042)	-4.012 (38.5260)

2. Secondary Outcome

Title	Model Adjusted Change From Baseline in Atheroma Volume to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Mean (Standard Error) [millimeters cubed (mm3)]	0.98 (2.001)	-3.60 (2.002)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean diff (RSG-GLP) for atheroma volume
	Estimated Value	-4.58
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Model Adjusted Change From Baseline in Lumen Volume to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Mean (Standard Error) [millimeters cubed (mm3)]	-4.91 (3.545)	-4.59 (3.526)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean diff (RSG-GLP) for lumen volume
	Estimated Value	0.32
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Model Adjusted Change From Baseline in Vessel Volume to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Mean (Standard Error) [millimeters cubed (mm3)]	-4.56 (3.479)	-8.13 (3.466)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean diff (RSG-GLP) for vessel volume
	Estimated Value	-3.56
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18
Description	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18
Time Frame	Baseline to Month 18

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Atheroma Area, Baseline	5.918 (2.9281)	5.748 (2.5585)
Atheroma Area, Month 18	5.928 (2.9615)	5.634 (2.5594)
Change from Baseline in Atheroma Area	0.010 (0.6448)	-0.114 (0.6990)
Vessel Area, Baseline	14.364 (5.1946)	14.166 (4.8231)
Vessel Area, Month 18	14.261 (5.1699)	13.977 (4.8595)
Change from Baseline in Vessel Area	-0.102 (1.1954)	-0.189 (0.9918)
Lumen Area, Baseline	8.447 (3.2037)	8.419 (3.2847)
Lumen Area, Month 18	8.335 (3.2056)	8.344 (3.3077)
Change from Baseline in Lumen Area	-0.113 (1.2166)	-0.075 (0.9207)

6. Secondary Outcome

Title	Model Adjusted Change From Baseline in Atheroma Area to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Mean (Standard Error) [millimeters square (mm2)]	0.03 (0.050)	-0.10 (0.050)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean diff (RSG-GLP) for atheroma area
	Estimated Value	-0.13
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Model Adjusted Change From Baseline in Lumen Area to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Mean (Standard Error) [millimeters square (mm2)]	-0.14 (0.079)	-0.11 (0.079)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean diff (RSG-GLP) for lumen area
	Estimated Value	0.02
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Model Adjusted Change From Baseline in Vessel Area to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Mean (Standard Error) [millimeters square (mm2)]	-0.10 (0.082)	-0.21 (0.082)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean diff (RSG-GLP) for vessel area
	Estimated Value	-0.11
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in Normalized Atheroma Volume
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Baseline	232.772 (115.1630)	226.075 (100.6261)
Month 18	233.153 (116.4765)	221.599 (100.6606)
Change from Baseline	0.381 (25.3600)	-4.476 (27.4901)

10. Primary Outcome

Title	Change From Baseline in Percent Atheroma Volume (PAV) to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Baseline	40.593 (10.9717)	40.422 (11.7506)
Month 18	41.013 (11.1572)	40.182 (11.4257)
Change from Baseline	0.420 (4.8085)	-0.240 (4.2421)

11. Primary Outcome

Title	Model Adjusted Change From Baseline in Percent Atheroma Volume (PAV) to Month 18
Description	Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior Oral Anti-Hyperglycemic Diabetic Medications(s) (OAD).
Time Frame	Baseline to Month 18

Outcome Measure Data

Analysis Population Description

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/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Mean (Standard Error) [percent (absolute change)]	0.43 (0.331)	-0.21 (0.331)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1221
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Model adjusted mean diff. (RSG-GLP)
	Estimated Value	-0.64
	Confidence Interval	() 95%; -1.457 to 0.173
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Model Adjusted Change From Baseline in Normalized Atheroma Volume
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Mean (Standard Error) [millimeters cubed (mm3)]	1.20 (1.974)	-3.92 (1.983)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Model adjusted mean diff. (RSG-GLP)
	Estimated Value	-5.12
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population with last observation carried forward (LOCF)

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Baseline	75.649 (32.6125)	70.961 (29.9610)
Month 18	72.225 (33.2887)	66.020 (30.7228)
Change from Baseline	-3.424 (11.9263)	-4.941 (12.2005)

14. Secondary Outcome

Title	Model Adjusted Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population with last observation carried forward (LOCF)

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Mean (Standard Error) [millimeters cubed (mm3)]	-3.56 (0.892)	-5.28 (0.898)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Model adjusted mean diff. (RSG-GLP)
	Estimated Value	-1.72
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population with last observation carried forward (LOCF)

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Baseline	7.569 (3.2718)	7.093 (3.0042)
Month 18	7.185 (3.2957)	6.625 (3.0741)
Change from Baseline	-0.384 (1.0608)	-0.468 (1.1370)

16. Secondary Outcome

Title	Model Adjusted Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline
Description	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

Outcome Measure Data

Analysis Population Description

IVUS Evaluable Population with last observation carried forward (LOCF)

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	229	233
Mean (Standard Error) [millimeters squared (mm2)]	-0.39 (0.081)	-0.50 (0.082)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Model adjusted mean diff. (RSG-GLP)
	Estimated Value	-0.11
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Model Adjusted Change in Glycated Hemoglobin (HbA1c) From Baseline to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	321	311
Mean (Standard Error) [Percentage]	-0.20 (0.051)	-0.30 (0.053)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	-0.10
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Model Adjusted Change in Fasting Plasma Glucose (FPG) From Baseline to Month 18
Description	From repeated measures analysis model: Change = Baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time Frame	Baseline to Month 18

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	273	255
Mean (Standard Error) [millimole/Liter (mmol/L)]	-0.46 (0.138)	-1.34 (0.145)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	-0.88
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Repeated Measures Analysis of Percent Change in hsCRP From Baseline to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	316	302
Adjusted Geometric Mean + Standard Error	-62.82 (-67.40)	-80.33 (-82.84)
Adjusted Geometric Mean	-65.18	-81.63
Adjusted Geometric Mean - Standard Error	-67.40	-82.84

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	-47.23
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Repeated Measures Analysis of Percent Change in MMP 9 From Baseline to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	298	291
Adjusted Geometric Mean + Standard Error	-26.5 (-34.3)	-38.8 (-45.5)
Adjusted Geometric Mean	-30.5	-42.2
Adjusted Geometric Mean - Standard Error	-34.3	-45.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	-16.9
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population with LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	212	199
Mean + Standard Error	1.141 (-13.764)	30.189 (11.683)
Mean	-6.608	20.582
Mean - Standard Error	-13.764	11.683

22. Secondary Outcome

Title	Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population with LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	212	199
Adjusted Geometric Mean + Standard Error	-4.865 (-17.465)	24.576 (7.499)
Adjusted Geometric Mean	-11.388	15.720
Adjusted Geometric Mean - Standard Error	-17.465	7.499

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio to GLP as % difference from GLP
	Estimated Value	30.591
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Percent Change From Baseline to Month 18 in Total Cholesterol (TC)
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	272	263
Adjusted Geometric Mean + Standard Error	-4.205	3.151
Adjusted Geometric Mean	-5.644	1.567
Adjusted Geometric Mean - Standard Error	-7.062	0.007

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	7.642
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Percent Change From Baseline to Month 18 in High Density Lipoprotein Cholesterol (HDL-c)
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	269	261
Adjusted Geometric Mean + Standard Error	7.208	15.104
Adjusted Geometric Mean	5.710	13.440
Adjusted Geometric Mean - Standard Error	4.233	11.808

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	7.316
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Percent Change From Baseline to Month 18 in HDL-2
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	269	260
Adjusted Geometric Mean + Standard Error	2.065	18.241
Adjusted Geometric Mean	-0.783	14.821
Adjusted Geometric Mean - Standard Error	-3.550	11.507

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	15.731
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Percent Change From Baseline to Month 18 in HDL-3
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	269	260
Adjusted Geometric Mean + Standard Error	10.683	15.165
Adjusted Geometric Mean	9.074	13.440
Adjusted Geometric Mean - Standard Error	7.490	11.732

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	3.998
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Percent Change From Baseline to Month 18 in Low Density Lipoprotein Cholesterol (LDL-c)
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	261	252
Adjusted Geometric Mean + Standard Error	-8.955	1.795
Adjusted Geometric Mean	-11.600	-1.237
Adjusted Geometric Mean - Standard Error	-14.172	-4.180

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	11.728
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

28. Secondary Outcome

Title	Percent Change From Baseline to Month 18 in Triglycerides (TG)
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	241	229
Adjusted Geometric Mean + Standard Error	-7.415	-13.601
Adjusted Geometric Mean	-10.309	-16.381
Adjusted Geometric Mean - Standard Error	-13.110	-19.067

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	-6.768
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Secondary Outcome

Title	Percent Change From Baseline to Month 18 in Free Fatty Acids (FFA)
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	236	229
Adjusted Geometric Mean + Standard Error	32.909	13.835
Adjusted Geometric Mean	27.303	8.880
Adjusted Geometric Mean - Standard Error	21.943	4.142

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	-14.478
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Secondary Outcome

Title	Percent Change From Baseline to Month 18 in Apoprotein B (apoB)
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	280	273
Adjusted Geometric Mean + Standard Error	-6.588 (-10.021)	-6.967 (-10.488)
Adjusted Geometric Mean	-8.320	-8.744
Adjusted Geometric Mean - Standard Error	-10.021	-10.488

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	-0.462
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

31. Secondary Outcome

Title	Change From Baseline to Month 18 in LDL-c Peak Particle Density Measured by LDL Relative Flotation
Description	From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time Frame	Baseline to Month 18

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	267	262
Mean (Standard Error) [Ratio]	0.0040 (0.00158)	0.0204 (0.001630)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	0.0164
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

32. Secondary Outcome

Title	Change From Baseline to Month 18 in Total Cholesterol/HDL-c Ratio
Description	From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time Frame	Baseline to Month 18

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	263	253
Mean (Standard Error) [ratio]	-0.495 (0.08380)	-0.377 (0.08620)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	0.118
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

33. Secondary Outcome

Title	Change From Baseline to Month 18 in LDL-c/HDL-c Ratio
Description	From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.
Time Frame	Baseline to Month 18

Outcome Measure Data

Analysis Population Description

ITT Population without LOCF

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	252	242
Mean (Standard Error) [ratio]	-0.365 (0.0610)	-0.226 (0.0629)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide (GLP) 5 mg, Rosiglitazone (RSG) 4 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference (RSG-GLP)
	Estimated Value	0.140
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

34. Secondary Outcome

Title	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)
Description	This was 1 of 2 MACE composite endpoints and was a secondary efficacy endpoint.
Time Frame	Baseline to Month 21

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	337	331
Number [Participants]	38 11.3%	39 11.8%

35. Secondary Outcome

Title	Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for Cardiovascular Death, Nonfatal MI, or Nonfatal Stroke (MACE Composite 2)
Description	This was 1 of 2 MACE composite endpoints and was a secondary efficacy endpoint.
Time Frame	Baseline to Month 21

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	337	331
Number [Participants]	10 3%	14 4.2%

36. Secondary Outcome

Title	Number of Other Cardiovascular Events
Description	This was one of the secondary endpoints of the study.
Time Frame	Baseline to Month 21

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Glipizide (GLP) 5 mg	Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months	Rosiglitazone (RSG) 4 mg once daily for 18 months
Measure Participants	337	331
All-cause death	7	8
Cardiovascular death	3	4
Non-fatal myocardial infarction	6	7
Non-fatal stroke	1	5
Coronary revascularization	27	26
Hospitalization for recurrent myocardial ischemia	7	11
Non-MACE congestive heart failure	3	8

Adverse Events

Arm/Group Title	Glipizide (GLP) 5 mg		Rosiglitazone (RSG) 4 mg
Arm/Group Description	Glipizide (GLP) 5 mg once daily for 18 months		Rosiglitazone (RSG) 4 mg once daily for 18 months
All Cause Mortality
	Glipizide (GLP) 5 mg		Rosiglitazone (RSG) 4 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Glipizide (GLP) 5 mg		Rosiglitazone (RSG) 4 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/337 (21.1%)		71/331 (21.5%)
Blood and lymphatic system disorders
Anaemia	1/337 (0.3%)		3/331 (0.9%)
Lymphadenitis	0/337 (0%)		1/331 (0.3%)
Cardiac disorders
Angina pectoris	10/337 (3%)		12/331 (3.6%)
Angina unstable	8/337 (2.4%)		4/331 (1.2%)
Coronary artery stenosis	3/337 (0.9%)		2/331 (0.6%)
Coronary artery disease	2/337 (0.6%)		1/331 (0.3%)
Acute coronary syndrome	2/337 (0.6%)		0/331 (0%)
Acute myocardial infarction	2/337 (0.6%)		0/331 (0%)
Myocardial infarction	1/337 (0.3%)		1/331 (0.3%)
Arrhythmia	0/337 (0%)		1/331 (0.3%)
Atrial flutter	1/337 (0.3%)		0/331 (0%)
Atrioventricular block second degree	0/337 (0%)		1/331 (0.3%)
Bradycardia	0/337 (0%)		1/331 (0.3%)
Cardiac arrest	0/337 (0%)		1/331 (0.3%)
Cardiac failure	0/337 (0%)		1/331 (0.3%)
Cardiac failure congestive	0/337 (0%)		1/331 (0.3%)
Cardiogenic shock	1/337 (0.3%)		0/331 (0%)
Cardiovascular disorder	1/337 (0.3%)		0/331 (0%)
Congestive cardiomyopathy	0/337 (0%)		1/331 (0.3%)
Palpitations	0/337 (0%)		1/331 (0.3%)
Prinzmetal angina	1/337 (0.3%)		0/331 (0%)
Ear and labyrinth disorders
Vertigo	1/337 (0.3%)		1/331 (0.3%)
Eye disorders
Macular hole	0/337 (0%)		1/331 (0.3%)
Gastrointestinal disorders
Colitis	1/337 (0.3%)		1/331 (0.3%)
Gastric ulcer	0/337 (0%)		2/331 (0.6%)
Abdominal pain	0/337 (0%)		1/331 (0.3%)
Abdominal pain upper	0/337 (0%)		1/331 (0.3%)
Gastric ulcer haemorrhage	0/337 (0%)		1/331 (0.3%)
Gastritis	1/337 (0.3%)		0/331 (0%)
Pancreatitis	1/337 (0.3%)		0/331 (0%)
Peritonitis	0/337 (0%)		1/331 (0.3%)
General disorders
Chest pain	8/337 (2.4%)		6/331 (1.8%)
Non-cardiac chest pain	4/337 (1.2%)		1/331 (0.3%)
Death	1/337 (0.3%)		1/331 (0.3%)
Fatigue	1/337 (0.3%)		0/331 (0%)
Ill-defined disorder	0/337 (0%)		1/331 (0.3%)
Oedema peripheral	0/337 (0%)		1/331 (0.3%)
Pyrexia	0/337 (0%)		1/331 (0.3%)
Sudden cardiac death	0/337 (0%)		1/331 (0.3%)
Vessel puncture site haemorrhage	0/337 (0%)		1/331 (0.3%)
Constipation	0/337 (0%)		1/331 (0.3%)
Dyspepsia	0/337 (0%)		1/331 (0.3%)
Enteritis	1/337 (0.3%)		0/331 (0%)
Gastrointestinal haemorrhage	1/337 (0.3%)		0/331 (0%)
Umbilical hernia	0/337 (0%)		1/331 (0.3%)
Hepatobiliary disorders
Biliary tract disorder	0/337 (0%)		1/331 (0.3%)
Cholecystitis acute	1/337 (0.3%)		0/331 (0%)
Cholelithiasis	1/337 (0.3%)		0/331 (0%)
Hepatitis toxic	0/337 (0%)		1/331 (0.3%)
Infections and infestations
Gastroenteritis	1/337 (0.3%)		1/331 (0.3%)
Bronchitis	1/337 (0.3%)		0/331 (0%)
Dengue fever	0/337 (0%)		1/331 (0.3%)
Erysipelas	0/337 (0%)		1/331 (0.3%)
Febrile infection	0/337 (0%)		1/331 (0.3%)
Influenza	0/337 (0%)		1/331 (0.3%)
Pneumonia	1/337 (0.3%)		0/331 (0%)
Respiratory tract infection	1/337 (0.3%)		0/331 (0%)
Septic shock	1/337 (0.3%)		0/331 (0%)
Urinary tract infection	0/337 (0%)		1/331 (0.3%)
Injury, poisoning and procedural complications
In-stent arterial restenosis	0/337 (0%)		3/331 (0.9%)
Post procedural myocardial infarction	0/337 (0%)		2/331 (0.6%)
Cervical vertebral fracture	1/337 (0.3%)		0/331 (0%)
Chest injury	1/337 (0.3%)		0/331 (0%)
Fall	0/337 (0%)		1/331 (0.3%)
In-stent coronary artery restenosis	1/337 (0.3%)		0/331 (0%)
Joint injury	1/337 (0.3%)		0/331 (0%)
Meniscus lesion	1/337 (0.3%)		0/331 (0%)
Muscle injury	0/337 (0%)		1/331 (0.3%)
Post procedural haematoma	0/337 (0%)		1/331 (0.3%)
Post procedural swelling	0/337 (0%)		1/331 (0.3%)
Postoperative thrombosis	1/337 (0.3%)		0/331 (0%)
Spinal fracture	0/337 (0%)		1/331 (0.3%)
Subdural haematoma	1/337 (0.3%)		0/331 (0%)
Therapeutic agent toxicity	0/337 (0%)		1/331 (0.3%)
Investigations
Cardiac enzymes increased	1/337 (0.3%)		0/331 (0%)
Metabolism and nutrition disorders
Dehydration	0/337 (0%)		1/331 (0.3%)
Diabetes mellitus inadequate control	1/337 (0.3%)		0/331 (0%)
Fluid retention	0/337 (0%)		1/331 (0.3%)
Gout	0/337 (0%)		1/331 (0.3%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	2/337 (0.6%)		0/331 (0%)
Gouty arthritis	1/337 (0.3%)		0/331 (0%)
Spinal osteoarthritis	1/337 (0.3%)		0/331 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of thyroid gland	0/337 (0%)		1/331 (0.3%)
Breast cancer in situ	1/337 (0.3%)		0/331 (0%)
Lung neoplasm malignant	0/337 (0%)		1/331 (0.3%)
Lymphoma	1/337 (0.3%)		0/331 (0%)
Malignant melanoma	1/337 (0.3%)		0/331 (0%)
Renal neoplasm	1/337 (0.3%)		0/331 (0%)
Nervous system disorders
Cerebrovascular accident	1/337 (0.3%)		2/331 (0.6%)
Loss of consciousness	1/337 (0.3%)		1/331 (0.3%)
Brain stem infarction	0/337 (0%)		1/331 (0.3%)
Carotid artery stenosis	1/337 (0.3%)		0/331 (0%)
Cerebral artery embolism	0/337 (0%)		1/331 (0.3%)
Dizziness	0/337 (0%)		1/331 (0.3%)
Presyncope	0/337 (0%)		1/331 (0.3%)
Syncope vasovagal	0/337 (0%)		1/331 (0.3%)
Vertebrobasilar insufficiency	0/337 (0%)		1/331 (0.3%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/337 (0.3%)		0/331 (0%)
Psychiatric disorders
Adjustment disorder with mixed disturbance of emotion and cond	1/337 (0.3%)		0/331 (0%)
Anxiety	0/337 (0%)		1/331 (0.3%)
Depression	1/337 (0.3%)		0/331 (0%)
Renal and urinary disorders
Renal failure acute	1/337 (0.3%)		1/331 (0.3%)
Calculus ureteric	1/337 (0.3%)		0/331 (0%)
Diabetic nephropathy	0/337 (0%)		1/331 (0.3%)
Nephroangiosclerosis	0/337 (0%)		1/331 (0.3%)
Proteinuria	0/337 (0%)		1/331 (0.3%)
Renal colic	0/337 (0%)		1/331 (0.3%)
Renal failure	1/337 (0.3%)		0/331 (0%)
Urinary incontinence	0/337 (0%)		1/331 (0.3%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/337 (0%)		1/331 (0.3%)
Prostatitis	0/337 (0%)		1/331 (0.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/337 (0.6%)		2/331 (0.6%)
Acute respiratory failure	0/337 (0%)		1/331 (0.3%)
Epistaxis	1/337 (0.3%)		0/331 (0%)
Hiccups	0/337 (0%)		1/331 (0.3%)
Hydrothorax	0/337 (0%)		1/331 (0.3%)
Pleural effusion	1/337 (0.3%)		0/331 (0%)
Pleurisy	0/337 (0%)		1/331 (0.3%)
Pulmonary embolism	1/337 (0.3%)		0/331 (0%)
Pulmonary oedema	1/337 (0.3%)		0/331 (0%)
Vascular disorders
Hypotension	0/337 (0%)		2/331 (0.6%)
Vascular pseudoaneurysm	2/337 (0.6%)		0/331 (0%)
Haematoma	0/337 (0%)		1/331 (0.3%)
Haemorrhage	1/337 (0.3%)		0/331 (0%)
Hypertension	1/337 (0.3%)		0/331 (0%)
Hypertensive crisis	1/337 (0.3%)		0/331 (0%)
Intermittent claudication	0/337 (0%)		1/331 (0.3%)
Thrombophlebitis	0/337 (0%)		1/331 (0.3%)
Other (Not Including Serious) Adverse Events
	Glipizide (GLP) 5 mg		Rosiglitazone (RSG) 4 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	117/337 (34.7%)		98/331 (29.6%)
Cardiac disorders
Angina pectoris	33/337 (9.8%)		31/331 (9.4%)
General disorders
Edema peripheral	24/337 (7.1%)		29/331 (8.8%)
Fatigue	13/337 (3.9%)		18/331 (5.4%)
Chest pain	17/337 (5%)		11/331 (3.3%)
Nervous system disorders
Dizziness	17/337 (5%)		16/331 (4.8%)
Headache	20/337 (5.9%)		11/331 (3.3%)
Respiratory, thoracic and mediastinal disorders
Cough	20/337 (5.9%)		13/331 (3.9%)
Vascular disorders
Hypertension	21/337 (6.2%)		13/331 (3.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.