1. Slide Source: www.lipidsonline.org Primary and Other Outcomes: DREAM Rosiglitazone group (n=2635) Placebo group (n=2634)HR (95% CI)p Composite primary outcome*306 (11.6%)686 (26.0%)0.40 (0.35-0.46)<0.0001 Diabetes280 (10.6%)658 (25.0%)0.38 (0.33-0.44) <0.0001 Diagnosed by FPG/OGTT231 (8.8%)555 (21.1%)0.38 (0.33-0.44)<0.0001 Physician diagnosed49 (1.9%)103 (3.9%)0.47 (0.33-0.66)<0.0001 Death30 (1.1%)33 (1.3%)0.91 (0.55-1.49)0.7 Regression (FPG <6.1 mmol/L)†1330 (50.5%)798 (30.3%)1.71 (1.57-1.87)<0.0001 Regression (FPG <5.6 mmol/L)†1016 (38.6%)540 (20.5%)1.83 (1.65-2.04)<0.0001 DREAM investigators. Lancet 2006;368:1096-1105. Data are number (%). *Rows are not mutually exclusive for components of the composite—if a participant had more than one component of the composite then they are counted in the relevant row. †Regression implies achieving a normal fasting glucose concentration (as defined in both rows) and 2-h plasma glucose level. FPG = fasting plasma glucose. OGTT = oral glucose tolerance test.

2. Slide Source: www.lipidsonline.org Primary and Other Outcomes: DREAM (cont’d) Rosiglitazone group (n=2635) Placebo group (n=2634) HR (95% CI)p Cardiovascular events composite*75 (2.9%)55 (2.1%)1.37 (0.97-1.94)0.08 Myocardial infarction15 (0.6%)9 (0.3%)1.66 (0.73-3.80) 0.2 Stroke7 (0.3%)5 (0.2%)1.39 (0.44-4.40)0.6 Cardiovascular death12 (0.5%)10 (0.4%)1.20 (0.52-2.77)0.7 Confirmed heart failure‡14 (0.5%)2 (0.1%)7.03 (1.60-30.9)0.01 New angina24 (0.9%)20 (0.8%)1.20 (0.66-2.17)0.5 Revascularization35 (1.3%)27 (1.0%)1.29 (0.78-2.14)0.3 Myocardial infarction, stroke, or cardiovascular death 32 (1.2%)23 (0.9%)1.39 (0.81-2.37)0.2 DREAM investigators. Lancet 2006;368:1096-1105. Data are number (%). *Rows are not mutually exclusive for components of the composite—if a participant had more than one component of the composite then they are counted in the relevant row. †Regression implies achieving a normal fasting glucose concentration (as defined in both rows) and 2-h plasma glucose level. ‡Defined as acute treatment with at least two of the following criteria: typical signs and symptoms, typical radiological evidence, use of diuretics, vasodilators, or inotropes.

3. Slide Source: www.lipidsonline.org Adverse Events, Hospitalization, and Death: ADOPT Variable Rosiglitazone (N=1456)Metformin (N=1454)Glyburide (N=1441) Serious Events Total Events Serious Events Total Events Serious Events Total Events Adverse events — number of patients (%) Total events346 (23.8)1338 (91.9)331 (22.8)1341 (92.2)308 (21.4)1321 (91.7) Cardiovascular disease49 (3.4)62 (4.3)46 (3.2)58 (4.0)26 (1.8)†41 (2.8) Myocardial Infarction Fatal2 (0.1) 3 (0.2) Nonfatal22 (1.5)25 (1.7)18 (1.2)21 (1.4)11 (0.8)15 (1.0) Congestive heart failure (investigator-reported)12 (0.8)22 (1.5)12 (0.8)19 (1.3)3 (0.2)†9 (0.6)† Stroke13 (0.9)16 (1.1)17 (1.2)19 (1.3)12 (0.8)17 (1.2) Peripheral vascular disease7 (0.5)36 (2.5)6 (0.4)27 (1.9)4 (0.3)31 (2.2) Gastrointestinal events8 (0.5)335 (23.0)7 (0.5)557 (38.3)‡3 (0.2)316 (21.9) Death and Hospitalization Hospitalization for any reason Patients — no. (%)169 (11.6)172 (11.8)150 (10.4) Events — no.251267203 Deaths from any cause—no.3431 ADOPT study group. N Engl J Med 2006;355:2427-2443. † P<0.05 for the comparison between this treatment group and the rosiglitazone group; ‡ P<0.01 for the comparison between this treatment group and the rosiglitazone group.

4. Slide Source: www.lipidsonline.org Laboratory Assessment and Concomitant Use of Cardiovascular Drugs: ADOPT Variable Rosiglitazone (N=1456)Metformin (N=1454)Glyburide (N=1441) Serious Events Total Events Serious Events Total Events Serious Events Total Events Laboratory assessment¶ ALT—IU/liter Mean21.424.9‡27.2‡ 95% CI20.6–22.224.1–25.826.3–28.1 ALT >3 times upper limit of normal — no. of patients (%)14 (1.0)16 (1.1)11 (0.8) LDL cholesterol — mg/dl Mean104.096.5‡99.3‡ 95% CI101.7–106.494.4–98.896.9–101.9 HDL cholesterol — mg/dl Mean51.850.5‡48.9‡ 95% CI51.3–52.450.0–51.048.3–49.5 Triglycerides — mg/dl Mean163.5166.5171.7† 95% CI159.2–167.9162.1–171.0166.8–176.9 Drugs used concomitantly — no. of patients (%) Lipid-lowering agents803 (55.2) 708 (48.7)‡ 651 (45.2)‡ Statins750 (51.5) 632 (43.5)‡ 579 (40.2)‡ Antihypertensive agents970 (66.6)969 (66.6)944 (65.5) ¶ All laboratory values are mean values at 4 years; † P<0.05 for the comparison between this treatment group and the rosiglitazone group; ‡ P<0.01 for the comparison between this treatment group and the rosiglitazone group. ADOPT study group. N Engl J Med 2006;355:2427-2443.

5. Slide Source: www.lipidsonline.org Rates of Myocardial Infarction and Death from Cardiovascular Causes Rosiglitazone Group Control Group Odds Ratio (95% CI)P Value no. of events/total no. (%) Myocardial Infarction Small trials combined44/10,285 (0.43)22/6106 (0.36)1.45 (0.88–2.39)0.15 DREAM 15/2,635 (0.57) 9/2634 (0.34)1.65 (0.74–3.68)0.22 ADOPT 27/1,456 (1.85)41/2895 (1.42)1.33 (0.80–2.21)0.27 Overall1.43 (1.03–1.98)0.03 Death from Cardiovascular Causes Small trials combined25/6,845 (0.36) 7/3980 (0.18)2.40 (1.17–4.91) 0.02 DREAM12/2,635 (0.46)10/2634 (0.38)1.20 (0.52–2.78)0.67 ADOPT2/1,456 (0.14)5/2895 (0.17)0.80 (0.17–3.86)0.78 Overall1.64 (0.98–2.74)0.06 Nissen and Wolski. N Engl J Med 2007;356:2457-2471.