1. VBWG PROactive: Study design Dormandy JA et al. Lancet. 2005;366:1279-89. Charbonnel B et al. Diabetes Care. 2004;27:1647-53. Objective: Assess the effects of pioglitazone on reducing macrovascular events in type 2 diabetes Design: Randomized, double-blind, placebo-controlled Population: N = 5238 with type 2 diabetes and history of macrovascular disease Treatment: Pioglitazone (up to 45 mg) or placebo Primary outcome: Composite of all-cause mortality, MI, ACS, coronary or peripheral revascularization, amputation, stroke Secondary outcomes: Individual components of primary outcome, CV mortality Follow-up: 4 years

2. VBWG PROactive: Baseline characteristics Charbonnel B et al. Diabetes Care. 2004;27:1647-53. Patient descriptionMean ± SD Age (yrs)61.8 ± 7.7 Male (%)66.1 Caucasian (%)98.5 Type 2 diabetes (yrs since onset)9.5 ± 7.0 Weight (lbs)194 ± 34 BMI (kg/m 2 )30.9 ± 4.8 Waist circumference (in)41.46 ± 4.7 Systolic BP (mm Hg)143.4 ± 17.8 Triglycerides (mg/dL)198.4 ± 158.8 HDL-C (mg/dL)44.9 ± 12 LDL-C (mg/dL)114.5 ± 37 A1C (%)8.08 ± 1.41

3. VBWG PROactive: CV medications at study entry Charbonnel B et al. Diabetes Care. 2004;27:1647-53.  -Blockers2859(55%) ACEI3286(63%) ARB356(7%) CCB1855(35%) Nitrates2058(39%) Thiazide830(16%) Antiplatelets 4394(84%) Aspirin3829(73%) Statins2135(41%) Fibrates448(9%) Current therapyn (%)

4. VBWG PROactive: Reduction in primary outcome Dormandy JA et al. Lancet. 2005;366:1279-89. Number at risk Pioglitazone24882373230222182146348 Placebo25302413231722152122345 5 10 15 25 0 6 20 01218243036 Pioglitazone (514 events) Placebo (572 events) Time from randomization (months) Proportion of events (%) All-cause mortality, nonfatal MI (including silent MI), ACS, revascularization, leg amputation, stroke *Unadjusted 10% RRR HR* 0.90 (0.80–1.02) P = 0.095

5. VBWG PROactive: Reduction in secondary outcome Dormandy JA et al. Lancet. 2005;366:1279-89. Number at risk Pioglitazone25362487243523812336396 Placebo25662504244223712315390 5 10 15 25 0 6 20 01218243036 Pioglitazone (301 events) Placebo (358 events) Time from randomization (months) Proportion of events (%) 16% RRR HR* 0.84 (0.72–0.98) P = 0.027 Combined nonfatal MI, all-cause mortality, stroke *Unadjusted

6. VBWG PROactive: Reduced need for insulin Dormandy JA et al. Lancet. 2005;366:1279-89. Number at risk Pioglitazone17001654160315541499244 Placebo16461544147214011325202 5 10 15 25 0 6 20 01218243036 Pioglitazone (183 events) Placebo (362 events) Time from randomization (months) Proportion of events (%) 53% RRR HR* 0.47 (0.39–0.56) P < 0.0001 *Unadjusted