1. Data Supplement RIO-Europe RIO-Lipids RIO-Diabetes RIO-North America European labeling

2. RIO-Europe: Study design N = 1507 BMI ≥30 kg/m 2 or >27 kg/m 2 with comorbidity* -600 kcal/day + advised to  PA Placebo Enrolled = 305 Completed = 178 Rimonabant 20 mg Enrolled = 599 Completed = 363 *Hypertension and/or dyslipidemia † Last observation carried forward Primary endpoint: Weight change from baseline † Secondary endpoints: Weight loss ≥5% and ≥10%, waist circumference, FG, fasting insulin, total-C, HDL-C, LDL-C, TG, MetS, HOMA-IR Follow-up: 1 year Van Gaal LF et al. Lancet. 2005;365:1389-97.

3. RIO-Europe: Treatment effect on weight and waist circumference Weeks (intent-to-treat population) LOCF *P ≤ 0.002 vs placebo LOCF = last observation carried forward ∆ WC (cm) PlaceboRimonabant 20 mg 0 -2 -4 -6 -8 -10 0 -2 -4 -6 -8 -10 012243652012243652 LOCF ∆ Body weight (kg) * *

4. Placebo RIO-Europe: Treatment effect on lipids Van Gaal LF et al. Lancet. 2005;365:1389-97. No significant effect on LDL-C or total-C *P ≤ 0.002 vs placebo 01224 Weeks (intent-to-treat population) LOCF3652 36LOCF01224 –10 –5 0 5 10 15 –15 30 25 20 15 10 5 0 * * ∆ HDL-C (%) ∆ TG (%) Rimonabant 20 mg

5. RIO-Europe: Adverse events Placebo (%) (n = 305) Rimonabant 20 mg (%) (n = 599) Nasopharyngitis15.715.5 Influenza10.59.0 Gastroenteritis7.98.5 Upper respiratory tract infection (URTI) 7.55.5 Bronchitis5.25.7 Sinusitis5.64.3 Headache13.49.8 Dizziness4.98.7 Nausea4.312.9 Diarrhea3.07.2 Arthralgia6.97.8 Back pain8.59.2 Fatigue5.64.2 Van Gaal LF et al. Lancet. 2005;365:1389-97. ≥5% incidence in any group

6. RIO-Lipids: Study design N = 1033 BMI 27-40 kg/m 2 with untreated dyslipidemia* -600 kcal/day + advised to  physical activity Placebo Enrolled = 342 Completed = 214 Rimonabant 20 mg Enrolled = 346 Completed = 221 *TG 150-700 and/or Total-C/HDL-C >4.5 (women) or >5 (men) † LOCF OGTT = oral glucose tolerance test Primary endpoint: Weight change from baseline † Secondary endpoints: HDL-C, TG, insulin, OGTT, MetS, leptin, adiponectin Follow-up: 1 year Després J-P et al. N Engl J Med. 2005;353:2121-34.

7. RIO-Lipids: Treatment effect on weight and WC Després J-P et al. N Engl J Med. 2005;353:2121-34. Intent-to-treat population ∆ Body weight (kg) Weeks 52 Placebo -10 0 243652012243612 Rimonabant 20 mg *P < 0.001 vs placebo ∆ WC (cm) 0 -2 -4 -8 -6 0 -2 -4 -8 -6 * *

8. RIO-Lipids: Treatment effect on lipids Després J-P et al. N Engl J Med. 2005;353:2121-34. Intent-to-treat population *P < 0.001 vs placebo No significant effect on LDL-C and total-C PlaceboRimonabant 20 mg ∆ HDL-C (%) Weeks 0 -20 ∆ TG level (%) 30 25 20 15 5 10 5 0 -5 -15 10 -10 243652012 243652012 * *

9. RIO-Lipids: Rimonabant weight-independent effect on adiponectin Després J-P et al. N Engl J Med. 2005;353:2121-34. 57% of adiponectin increase was independent of weight loss PlaceboRimonabant 20 mg ∆ Adiponectin level (  g/mL) 0 4 3 1 2 0–55–10≥10Weight gain Weight loss (%)

10. RIO-Lipids: Adverse events Placebo (%) (n = 342) Rimonabant 20 mg (%) (n = 346) Nasopharyngitis21.619.4 Headache15.815.3 Nausea3.212.7 Dizziness6.710.4 Influenza5.39.5 URTI9.98.7 Anxiety3.88.7 Back pain10.27.2 Diarrhea4.17.2 Gastroenteritis6.46.6 Insomnia2.66.4 Arthralgia9.65.5 ≥5% incidence in any group Després J-P et al. N Engl J Med. 2005;353:2121-34.

11. RIO-Diabetes: Study design N = 1047 T2DM, BMI 27–40 kg/m 2, A1C 6.5%–10%, and FG 100–271 mg/dL -600 kcal/day + advised to  PA Placebo Enrolled = 348 Completed = 231 Rimonabant 20 mg Enrolled = 339 Completed = 229 Scheen AJ et al. Lancet. 2006;368:1660-72. *LOCF Primary endpoint: Weight change from baseline* Secondary endpoints: A1C, HDL-C, TG, FG, fasting insulin, hsCRP, leptin, MetS, waist circumference, BP Follow-up: 1 year

12. 0 -5 -10 -15 0 -3 RIO-Diabetes: Treatment effect on weight and waist circumference WeightWaist circumference P < 0.0001 Scheen AJ et al. Lancet. 2006;368:1660-72. Δ Body weight (lb) Δ WC (in) 012243652 Week 012243652 Week -2 Intent-to-treat population PlaceboRimonabant 20 mg/day

13. Δ from baseline (%) RIO-Diabetes: Treatment effect on lipids No significant effect on LDL-C and total-C Scheen AJ et al. Lancet. 2006;368:1660-72. 20 15 10 5 0 0 -5 -15 -20 HDL-CTriglycerides P < 0.0001 Δ from baseline (%) 012243652 Week 012243652 Week 5 -10 PlaceboRimonabant 20 mg

14. RIO-Diabetes: Treatment effect on glucose metabolism A1C Δ from baseline (%) Δ from baseline HOMA-IR P < 0.0001 P = 0.03 PlaceboRimonabant 20 mg Scheen AJ et al. Lancet. 2006;368:1660-72.

15. RIO-Diabetes: Adverse events Placebo (%) (n = 348) Rimonabant 20 mg (%) (n = 339) Nausea612 Nasopharyngitis2112 Dizziness59 Arthralgia89 Headache98 Diarrhea77 Back pain77 URTI97 Vomiting26 Hypoglycemia25 Fatigue45 Anxiety35 ≥5% incidence in any group Scheen AJ et al. Lancet. 2006;368:1660-72.

16. RIO-North America: Study design N = 3045 BMI ≥30 kg/m 2 or >27 kg/m 2 with comorbidity Year 1 Rimonabant 20 mg Enrolled = 1222 Completed = 673 Year 1 Placebo Enrolled = 607 Completed = 309 Pi-Sunyer FX et al. JAMA. 2006;295:761-75. Year 2 Placebo Enrolled = 327 Completed = 225 Year 2 Rimonabant 20 mg Enrolled = 333 Completed = 257 Year 2 Placebo Enrolled = 299 Completed = 214 Primary endpoints: Weight change from baseline; prevention of weight regain* Secondary endpoints: Weight loss ≥5% or ≥10%, waist circumference, lipids, MetS, BP, FG, fasting insulin, HOMA-IR *LOCF

17. RIO-North America: Weight change by treatment assignment Pi-Sunyer FX et al. JAMA. 2006;295:761-75. Intent-to-treat population Δ Body weight (kg) Weeks 52 0 -2 -4 -8 -6 -10 0243612 Year 1Year 2 104 0 -2 -4 -8 -6 -10 52768864 PlaceboRimonabant 20 mg Rimonabant 20 mg/PlaceboRimonabant 20 mg/Rimonabant 20 mg Placebo/Placebo

18. RIO-North America: Waist circumference by treatment assignment Pi-Sunyer FX et al. JAMA. 2006;295:761-75. Δ WC (cm) Weeks 52 0 -2 -4 -8 -6 -10 0243612 Year 1Year 2 104 0 -2 -4 -8 -6 -10 52768864 PlaceboRimonabant 20 mg Rimonabant 20 mg/PlaceboRimonabant 20 mg/Rimonabant 20 mg Placebo/Placebo

19. RIO-North America: Treatment effect on lipids at 1 year Pi-Sunyer FX et al. JAMA. 2006;295:761-75. No significant effect on LDL-C or total-C PlaceboRimonabant 20 mg ∆ HDL-C (mg/dL) Weeks -2 -30 ∆ TG (mg/dL) 10 8 6 4 0 5 0 -5 -10 -20 2 -15 243652012 243652012 -25

20. -15 -10 -5 0 5 10 Change (%) RIO-North America: Weight-independent and weight-dependent effects on lipids Pi-Sunyer FX et al. JAMA. 2006;295:761-75. HDL-C TG 42% Weight-dependent effect 58% Weight-independent effect 53% Weight-dependent effect 47% Weight-independent effect Rimonabant 20 mg vs placebo ANCOVA

21. RIO-North America: Weight-independent and weight-dependent effects on insulin and IR Δ (  U/mL) 50% Weight- dependent 50% Weight- independent Δ 49% Weight- dependent 51% Weight- independent Pi-Sunyer FX et al. JAMA. 2006;295:761-75. Rimonabant 20 mg vs placebo ANCOVA

22. RIO-North America: Adverse events Placebo (%) (n = 498) Rimonabant 20 mg (%) (n = 1042) URTI15.218.5 Nasopharyngitis14.017.0 Nausea5.811.2 Arthralgia8.28.8 Sinusitis11.78.7 Headache10.27.8 Back pain6.15.9 Influenza7.78.8 Diarrhea5.15.3 Viral gastroenteritis4.85.7 ≥5% incidence in any group Pi-Sunyer FX et al. JAMA. 2006;295:761-75.

23. RIO-North America: Adverse events, cont’d Placebo (%) (n = 498) Rimonabant 20 mg (%) (n = 1042) Dizziness4.05.6 Anxiety2.16.1 Bronchitis5.14.3 Depressed mood3.15.2 Fatigue3.65.2 Insomnia4.45.8 ≥5% incidence in any group Pi-Sunyer FX et al. JAMA. 2006;295:761-75.

24. Obesity program* depression-related events: Overall incidences Depressed mood disorders and disturbances Mood alterations with depressive symptoms Depressive disorders 4.5 2.8 1.7 6.3 3.6 2.8 8.4 4.7 3.9 Placebo N = 2472 (%) 5 mg N = 2520 (%) 20 mg N = 2742 (%) Rimonabant *Obesity program (RIO-Europe, RIO-North America, RIO-Lipids, RIO-Diabetes, REBA, EFC5745 and ACT3801) Taking into account any patient exposure Data on file from sanofi-aventis.

25. Completed phase 2 and 3 studies* as of March 2007: All suicidality-related events Definitely suicidal (suicidal behavior/ideation) Possibly suicidal Rimonabant *Phase 2 studies: ACT4389, DRI3388, ACT4855, Metatrial study (DFI3077, DFI3024, DFI3067, DFI3138), PDY3796, DRI5747 and Phase 3 studies: RIO-Europe, RIO-North America, RIO-Lipids, RIO-Diabetes, REBA, SERENADE, EFC5745, ACT3801 and EFC4474, EFC4796, EFC4964, EFC5794, EFC4798 † Originally reported as a completed suicide but adjudicated as not enough information, fatal Using first randomized treatment 21 2 Placebo N = 3411 N (%) 11 1 † 5 mg N = 5254 N (%) 0000 10 mg N = 198 N (%) 48 5 20 mg N = 7851 N (%) 0000 40 mg N = 206 N (%) (0.62) (0.06) (0.21) (0.02) (0) (0.61) (0.06) (0) Data on file from sanofi-aventis.

26. Rimonabant clinical safety: Summary Safety assessment based on extensive exposure up to 2 years The most frequent adverse events that led to drug discontinuation were depression, mood alteration, nausea and anxiety Psychiatric events: –Increased incidence of depression-related events and anxiety with rimonabant vs placebo, overall incidence remained relatively low –Most adverse events were mild to moderate intensity –Similar qualitative characteristics between rimonabant 20 mg vs placebo No clinical changes in laboratory test, electrocardiogram, or vital signs Long-term exposure did not identify new or increased risks and supports its long term administration in overweight/obese patients with at least one cardiometabolic risk factor Data on file from sanofi-aventis.

27. ACOMPLIA: European product information Therapeutic indication As an adjunct to diet and exercise for treatment of patients with BMI ≥30 kg/m 2 or >27 kg/m 2 with associated risk factors such as T2DM or dyslipidemia Adult dosing 20 mg daily, to be taken in the morning before breakfast No dosage adjustment in elderly, mild/moderate hepatic insufficiency, or mild/moderate renal impairment European Medicines Agency (EMEA). http://emea.europa.eu.

28. ACOMPLIA: European product information, cont’d Contraindicated/Not recommended Pregnant or breast-feeding women Children below age 18 years Uncontrolled serious psychiatric illness such as major depression Taking antidepressant medication Severe renal or hepatic impairment Use with caution Receiving potent CYP3A4 inhibitors –Ketoconazole –Itraconazole –Ritonavir –Telithromycin –Clarithromycin –Nefazodone Treated for epilepsy Moderate hepatic impairment Age >75 years EMEA. http://emea.europa.eu.