1. RENAAL Baseline Characteristics (I) Age, years Male, % Female, % Race, % Asian Black Caucasian Hispanic Other Systolic (mmHg) Diastolic (mmHg) BMI (kg/m 2 ) % Losartan (+CT) (n=751) 60 62 39 16 17 48 19 2 152 82 30 Placebo (+CT) (n=762) 60 65 35 18 14 50 18 1 153 82 29 Brenner BM et al New Engl J Med 2001;345(12):861-869.

2. RENAAL Baseline Characteristics (II) Medical History Treatment for Hypertension Angina Pectoris Myocardial Infarction Coronary Revascularization Stroke Lipid Disorders Amputation Neuropathy Retinopathy Smoking (current) Losartan (+CT) (n=751) % 92 9 10 0.1 0 31 9 50 66 20 Placebo (+CT) (n=762) % 95 10 12 0.1 36 9 50 62 17 Brenner BM et al New Engl J Med 2001;345(12):861-869.

3. RENAAL Baseline Characteristics (III) Laboratory Urinary alb:creat (median) (mg/g) Serum Creatinine (mg/dL) Serum Cholesterol (mg/dL) Total LDL HDL Serum Triglycerides (mg/dL) Hemoglobin (g/dL) Glycosylated Hemoglobin (%) Losartan (+CT) (n=751) 1237 1.9 227 142 45 213 12.5 8.5 Placebo (+CT) (n=762) 1261 1.9 229 142 45 225 12.5 8.4 p=NS for all values Brenner BM et al New Engl J Med 2001;345(12):861-869.

4. RENAAL Primary Components ESRD Months 012243648 % with event 0 10 20 30 p=0.002 Risk Reduction: 28% P (+CT) L (+CT) ESRD or Death P (+ CT) L (+ CT) Months % with event 0122436 48 0 10 20 30 40 50 751714625 37569 762715610 34742 P (+CT) L (+CT) p=0.01 Risk Reduction: 20% Doubling of Serum Creatinine Months % with event p=0.006 Risk Reduction: 25% 751692583329 52 762689554 295 36 P (+ CT) L (+ CT) 012243648 0 10 20 30 P (+CT) L (+CT) P (+ CT) L (+ CT) 751714 625 37569 762715 610 34742 Brenner BM et al New Engl J Med 2001;345(12):861-869.

5. RENAAL First Hospitalization for Heart Failure 012243648 Months 0 5 10 15 20 % with event Risk Reduction: 32% p=0.005 P (+CT) L (+CT) 76268561637553 75170163738874 P (+CT) L (+CT) Brenner BM et al New Engl J Med 2001;345(12):861-869.

6. RENAAL Change from Baseline in Proteinuria Proteinuria measured as the urine albumin:creatinine ratio from a first morning void. 012243648 Months Median Percent Change -60 -40 -20 0 20 40 751661558438167 p<0.001 P (+CT) L (+CT) 762632529390130 P (+CT) L (+CT) 35% Overall Reduction Brenner BM et al New Engl J Med 2001;345(12):861-869.

7. insufficiency RENAAL Most Common Clinical and Laboratory Adverse Experiences Leading to Discontinuation of Study Therapy HeartESRDMyocard.StrokeWorseningsCrHyper- Failureinfarction renalincreasedkalemia 0 2 4 6 Percentage Laboratory AE Clinical AE 3% 6% 2% 3% 1% 2% 1% 1.5% 1.2%1.1% 0.5% Losartan Placebo (+CT) Presented by Brenner B. Reduction of endpoints in non-insulin-dependent diabetes mellitus with angiotensin II antagonist losartan. Program and abstracts of the 16th Annual Meeting of the American Society of Hypertension; May 16-19, 2001; San Francisco, California

8. RENAAL Summary In patients with Type 2 diabetes and nephropathy:In patients with Type 2 diabetes and nephropathy: –losartan delayed the onset of the primary composite endpoint (DsCr/ESRD/Death) and delayed the progression to ESRD. –losartan reduced proteinuria and the rate of decline in renal function (1/sCr slope). –losartan reduced the incidence of hospitalization for heart failure. –these benefits were largely independent of achieved blood pressure. –losartan and placebo, on a background of conventional therapy, showed no significant difference on all-cause mortality, MI, stroke, revascularization, hospitalizations for unstable angina, and death due to CV disease. –losartan was generally well tolerated in this patient population. Brenner BM et al New Engl J Med 2001;345(12):861-869.