1. Saint Denis 28 Octobre 2006 TRAITEMENT PHARMACOLOGIQUE Principes, état de la question, futur Pr O. ZIEGLER Nancy
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5. Poids Placebo Médicament 3 – 6 mois 1 an 2 ans - 10 % Arrêt Temps Prise du médicament 1 2 baseline T 0 Run in Tirage au sort O. Ziegler, B. Guy-Grand 2003 Perte de poids Stabilisation
6. XENDOS : Weight Loss with Orlistat is Sustained Over 4 Years - 4.1 kg - 6.9 kg P < 0.001 0 52 104 156 208 -12 -9 -6 -3 0 Placebo + lifestyle Xenical + lifestyle Week Change in weight (kg) Torgerson, Sjöstrom et al. Diabetes Care 2004 Completers : 34 % 52 %
7. STORM – Mean bodyweight changes during weight loss and weight maintenance phases over 2 years 104 102 100 98 96 94 92 90 88 0 12 2 4 6 8 10 14 16 18 20 22 24 Month Weight (kg) Placebo Sibutramine 10 mg 20mg Randomisation Sib 10 mg n = 115 n = 352 James et al, 2000 Lancet (endpoint) 52%
8. Consistent Weight Change Pooled data from: L.Van Gaal, Lancet 2005, X. Pi-Sunyer, JAMA 2006, JP. Després, NEJM 2005 Weight change (kg) Weeks * For RIO EU, completers plateau -10 -8 -6 -4 -2 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 LOCF RIO~Europe Placebo R 20 mg RIO~Lipids Placebo R 20 mg RIO~NA Placebo R 20 mg -8.6 kg* -3.6 kg*
11. Changes in CV risk factors in Orlistat responders with or without Metabolic Syndrome No MS MS O. Ziegler ECO 2005 <0.05 <0.05 <0.05 Waist (cm) TG (%) DBP (mmHg) SBP (mmHg) Glyc (mmol/L) LDL-C (%) HDL-C (%) Weight (%) – 11.5 – 10.1 – 1 +4.8 – 11.5 – 0.03 – 2.8 – 1.7 – 11.9 – 11.3 – 14.4 +9.9 – 9.2 – 0.11 – 7.4 – 5.7 NS <0.05 <0.05 <0.05 NS NS <0.05
12. Sibutramine : STORM –24 months Effects on Metabolic Parameters, from baseline Placebo James WPT et al , Lancet 2000; 356: 2119-25 N Finer, Eur Heart J 2005, 7, L 32 The rise in HDL-chol seems to be partially independent of weight loss STORM Sibutramine 20.7 -18.5 11.7 - 3.75 -25 -20 -15 -10 -5 0 5 10 15 20 25 HDL-C TG Mean % Change
13. RIO~program: Reduction in Metabolic Syndrome OR=0.541 ( p <0.001) OR=0.440 ( p <0.001) OR=0.429 (p<0.001) OR=0.597 ( p =0.007) -39.1% -53.6% -18.9% -51.2% -7.9% -21.3% -21% -7.6% ITT, LOCF Placebo Rimonabant 20 mg
14. Hollander , et al. 1998; Finer 2005 DIABETES : Mean change in HbA1c % according to Weight loss (% or kg) SIBUTRAMINE 15 mg ORLISTAT Metformin (Mc Nulty 2003) - 1 - 2 - 3 Gain / 0 - 5 % 5 - 10 % > 10 % Placebo Orlistat 360 mg
15. Hollander , et al. 1998; Finer 2006, Scheen 2005 - 1 - 2 - 3 Gain / 0 - 5 % 5 - 10 % > 10 % Placebo Orlistat 360 mg ≤ -2 DIABETES : Mean change in HbA1c % according to Weight loss (% or kg) SIBUTRAMINE -2 to 2 2 to 6 6 to10 Placebo 20mg rimonabant Weight loss (kg) n=29 n=7 n=55 n=68 n=125 n=79 n=57 n=10 n=161 n=41 ≥ 10 ITT population -1,2 -1,0 -0,8 -0,6 -0,4 -0,2 0,0 0,2 0,4 0,6 0,8
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18. Long term weight loss with Sibutramine (15 mg) Intermittent vs continuous therapy Wirth, A. et al. JAMA 2001;286:1331-1339 . Randomisation if WL 2 % or 2 kg at 1 month 3.8 kg 7.8 kg 48 week Sib 15 mg ITT 4 4 W discontinuation
19. Early Weight Loss with Orlistat Predicts Long-term Success - 4 0 12 24 36 52 -20 -10 0 - 6.0% - 14.5% Week < 5% 12-week weight loss > 5% 12-week weight loss Mean weight change (%) Rissanen A et al. IJO 1999 Early responders
20. Chanoine, J.-P. et al. JAMA 2005;293:2873-2883 . Change in Mean Body Mass Index and Weight Adolescents : Orlistat (120 mg 3x/j) + Thérapie comportementale + déficit ~500 kcal/j – USA, Canada Filles : 71 % , Caucasiens : 78 % - Age : 13,5 ans IMC : 35,4, 95 kg pour 1,64 m + 0,31 - 0,55 + 3,1 + 0,5 Taille : + 2 cm COMPLETERS Orlistat : 65 % Placebo : 64 %
21. Adolescents : sibutramine (10-15 mg/j) + Thérapie comportementale + déficit 500 kcal/j - USA Age : 12 -16 ans IMC > 2 /95 perc Mais < 44 kg/m 2 Age : 13,5 ans IMC : 36 kg/m 2 IMC > 37 : 38 % 98 kg pour 1,65m Filles : 64 % , Caucasiens : 57 % - 2,9 kg/m 2 - 8,4 kg Berkowitz RI, Ann Intern Med 2006
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23. THE SPECTRUM OF OBESITY MANAGEMENT ROLE OF PHARMACOTHERAPY PREVENTION OF WEIGHT GAIN OBESITY DRUG For responders 1 2 3 DIET EXERCISE LIFESTYLE MODIFICATIONS BEHAVIOUR from IOTF modified, 1997 WEIGHT MAINTENANCE MANAGEMENT of CO-MORBIDITIES WEIGHT LOSS ? Size = relative contribution to effective control of obesity
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