1. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 1 Dual Inhibition of Two Sources of Cholesterol: Absorption and Production in Patients with Type 2 Diabetes Results of a Clinical Trial with Ezetimibe Coadministered with Simvastatin vs. Simvastatin Alone

2. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 2 Study Design Design –Multicenter, double-blind, randomized, 24-week study following a 6-week run-in period during which all patients received simvastatin 20 mg/day Treatment groups –Ezetimibe + Simvastatin* 20 mg once daily (n=104) –Simvastatin 40 mg once daily (n=110) Selected entry criteria –Age 30 to 75 years –Type 2 diabetes mellitus (HbA 1c  9.0%) –Prior treatment with thiazolidinediones –LDL-C  100 mg/dl (  2.58 mmol/L) prior to initiation of simvastatin therapy *Eze+Simva in this presentation. Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

3. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 3 Endpoints Primary –Percent change from baseline in plasma LDL-C Key secondary –Percentage of patients reaching target LDL-C levels of <100 mg/dl (<2.58 mmol/L) –Percent change from baseline in other lipoproteins, lipids, and apolipoproteins Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

4. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 4 Baseline Characteristics Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004. Eze+ Simva 20 mg (n=104) Simvastatin 40 mg (n=110) Age Mean (years) Range 58 35–80 58 37–78 GenderMale (% of patients)Female 60 40 55 45 RaceWhite (% of patients) Hispanic Black Other 53 24 15 8 55 27 12 6 LipidsMean LDL-C (mg/dl) 94 91 Mean total cholesterol (mg/dl)172168 Mean HDL-C (mg/dl) 47 49 Median triglycerides (mg/dl) 150152 DiabetesMean BMI (kg/m 2 ) parametersMean HbA 1c (%) Mean fasting serum glucose (mg/dl) Mean fasting serum insulin (µlU/ml) 33 7 142 15 34 7 147 14

5. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 5 LDL-C Reduction from Simvastatin Baseline *p<0.001 vs. simvastatin Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004. Mean % change from baseline at 24 weeks 0 –10 –15 –20 –5 Simvastatin 40 mg (n=110) –0.3 Eze+ Simva 20 mg (n=104) –21* –25

6. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 6 Percentage of Patients Who Achieved LDL-C Goal of <100 mg/dl % Patients** 80 10 Simvastatin 40 mg (n=33) 39 Eze+ Simva 20 mg (n=37) 76* 0 20 30 40 50 60 70 *p<0.001 vs. simvastatin **Subgroup of patients who were not at goal at randomization (baseline) following six weeks of treatment with simvastatin 20 mg/day Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

7. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 7 Reductions in Other Lipids from Simvastatin Baseline *p<0.001 vs. simvastatin Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004. LS mean % change from baseline 0 –10 –15 –20 –5 –25 Eze+Simva 20 mg (n=104) Simvastatin 40 mg (n=110) Total cholesterol –2 –15* Apolipoprotein B –2 –14* Non–HDL-C –2 –20*

8. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 8 *Based on investigator assessment of dipstick results **Asymptomatic and transient Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004. Adverse Events of Interest % of Patients Eze+ Simva 20 mg (n=104) Simvastatin 40 mg (n=110) Clinical Anemia Edema Weight gain Myopathy 15101510 45004500 Laboratory Increased HbA 1c Increased fasting blood sugar Proteinuria* ALT  3  ULN (consecutive) AST  3  ULN (consecutive) CPK  10  ULN 1 0 1 0 1** 3 2 0 <1 0

9. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 9 Dual Inhibition of cholesterol absorption and production with Eze+Simva 20 mg was more effective than doubling the dose of simvastatin to 40 mg Greater LDL-C reduction (p<0.001) More patients achieved LDL-C goal (p<0.001) Greater improvements in overall lipid profile (total cholesterol, apolipoprotein B, non–HDL-C) Similar effects on HDL-C and triglycerides Similar safety and tolerability profile Conclusions Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

10. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 10 References Please refer to notes page.

11. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 11 Dual Inhibition of Two Sources of Cholesterol: Absorption and Production in Patients with Type 2 Diabetes Before prescribing, please consult the manufacturers’ prescribing information. MSP does not recommend the use of any product in any different manner than as described in the prescribing information. Copyright © 2004 MSP Singapore Company, LLC. All rights reserved.5-05 EZT 2004-W-6143-SS Printed in USA