Vanguard Phase Results for the Blood Pressure Component Presented at the American Diabetes Association 68th Scientific Sessions on June 10, 2008.

Vanguard BP Participants (N=491) Baseline Characteristics Mean or % Age (yrs) 63 BMI (kg/m2) 32 Race / Ethnicity Creatinine (mg/dL) 1.0 White % 52 eGFR (mL/min/1.73m2) 99 Black % 30 2° prevention, % Hispanic % 11 Current smoking % 12 Minority % 51 On Antihypertensive % 83 Women % On Thiazides % 19 DM Duration (yrs) 10 On ACE Inhibitor % 55 A1C (%) 8.7 On ß-Blocker % 15 3

Blood Pressure Protocol Various drugs/combinations provided to achieve goal BP according to randomized assignment. 2-drug therapy initiated in Intensive BP group: thiazide-type diuretic + ACEI, ARB, or ß-blocker. Drugs added and/or titrated at each visit to achieve BP goals. In Intensive group, at periodic “Milepost” visits addition of another drug “required” if not at goal. Down-titration in Standard group if SBP: <135 mm Hg on 2 consecutive visits or <130 mm Hg at one visit

Milepost Visit Approach for Intensive BP Participants Start 1 2 3 4 mos 5 6 7 Entry Milepost Visit SBP: 134 On meds: 2 Add: CCB Total: 3 SBP: 152 On meds: 0 Start: Diuretic/ACE Total: 2 8 mos 12 mos 9 10 11 Milepost Visit Milepost Visit SBP: 122 On meds: 3 Add: Reserpine Total: 4 SBP: 114 On meds: 4 Add: 0 Total: 4

Vanguard SBP Distribution for Intensive Group 12+16 mo mean = 121 mm Hg BL mean = 142 mm Hg Restricted to 211 participants with measurements at all 3 visits

Achieved Systolic Pressures in VG Means +/- 95% Confidence Intervals Mean # Meds: 1.5 1.7 1.8 1.9 1.8 Mean # Meds: 1.9 2.4 2.8 3.0 3.1 Points of Emphasis / Key Messages The risk of cardiovascular death is substantially increased in patients with type 2 diabetes and comorbid elevated SBP. For an SBP of 120 to 139 mm Hg, concurrent diabetes is equivalent to adding 40 mm Hg to the systolic pressure. In addition, MRFIT demonstrated that SBP (as well as elevated serum cholesterol levels and cigarette smoking) is a significant predictor of mortality in men with and without diabetes. The Multiple Risk Factor Intervention Trial (MRFIT) enrolled 361,662 men 35 to 37 years of age. A total of 5625 were receiving treatment for diabetes; the remaining 356,037 did not have diabetes. The study did not classify diabetes as insulin-dependent or non-insulin-dependent (NIDDM), but because of the participants’ age, more than 90% were assumed to have NIDDM.  Men whose SBP was ³180 mm Hg had nearly twice the risk of CV mortality if they had diabetes. If SBP was 140 to 179 mm Hg, the risk was more than twice that of men with diabetes.  Reference Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16:434-444. 7

SBP Delta between Treatment Arms in Vanguard Means & 95% Confidence Intervals 8

Vanguard Medication Use by Class 16 Month Visit * thiazide diuretics: intensive: 74%, standard:41%

Vanguard DBP Distribution for Intensive Group BL mean = 76 mm Hg 12+16 mo mean = 66 mm Hg Restricted to 211 participants with measurements at all 3 visits

UKPDS, ADVANCE, and ACCORD BP reduction in context: UK Prospective Diabetes Study Epidemiologic Data SBP UK Prospective Diabetes Study 11

Vanguard BP Conclusions Achieved SBPs and delta SBP between randomized groups supported continuation of the ACCORD BP trial into the full-scale trial. With this treatment algorithm SBP was lowered to an average of 120 mm Hg in patients with type 2 DM over 16 months, using an average of about 3 medications. The data suggest ACCORD will provide definitive clinical trial data on possible benefits and risks of treating to lower BP goals in patients with type 2 DM.