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Principles of Pharmacotherapy in the Management of Obesity Drugs Approved by FDA for Treating Obesity Generic Name Trade Names DEA Schedule Approved Use Year Approved Orlistat Xenical None Long-term 1999 Sibutramine Meridia IV Long-term 1997 Diethylpropion Tenulate IV Short-term 1973 Phentermine Adipex, lonamin IV Short-term 1973 Phendimetrazine Bontril, Prelu-2 III Short-term 1961 Benzphetamine Didrex III Short-term 1960 Effect of Continuous and Intermittent Phentermine Therapy on Body Weight Alternate Phentermine and Dummy 0 4 8 12 16 20 24 Time (weeks) Munro JF et al. Brit Med J 1:352, 1968 Weight Loss (lbs) Continuous Dummy Continuous Phentermine 28 32 36 Orlistat Prevents Fat Digestion and Absorption by Binding to Gastrointestinal Lipases Bile Acids Micelle TG=triglyceride; MG=monoglyceride; FA=fatty acid. Mucosal Cell LIPASE FA MG Intestinal Lumen Orlistat TG 0 200 400 600 800 1000 1200 Orlistat Daily Dose (mg) Effect of Orlistat Dose on Fecal Fat Excretion Fecal Fat Excretion (% intake) Zhi et al. Clin Pharmacol Ther 1994;56:82. -4.1 kg -6.9 kg P0.001 vs placebo Effect of Long-term Orlistat Therapy on Body Weight 0 52 104 156 208 Weeks Torgenson et al. Diabetes Care 2004;27:155 Change in Weight (kg) Placebo Orlistat Study or Sub-category WMD (random) 95% CI Hollander 1998* Sjostrom 1998 Davidson 1999 Finer 2000 Heuptman 2000 Lindgarde 2000 Rossner 2000 Bakris 2002 Broom 2002 Kelley 2002* Miles 2002* Total (95% CI) Meta-analysis of RCTs Evaluating Effect of Orlistat Therapy on Weight Loss at 1-Year *All subjects had type 2 diabetes WMD=weighted mean difference Padwal et al. Int J Obes 2003;27:1437 -10 -5 Favours Treatment 5 Favours Control 10 0 Weight Loss Category (%initial body weight) *P 0.01 vs placebo . Data pooled from 5 trials (N = 1773) . Segal et al. FASEB J. 1999;13:A