Principles of Pharmacotherapy in the Management of ObesityDrugs Approved by FDA for Treating ObesityGeneric NameTrade NamesDEA ScheduleApproved UseYear ApprovedOrlistatXenicalNoneLong-term1999SibutramineMeridiaIVLong-term1997DiethylpropionTenulateIVShort-term1973PhentermineAdipex, lonaminIVShort-term1973PhendimetrazineBontril, Prelu-2IIIShort-term1961BenzphetamineDidrexIIIShort-term1960Effect of Continuous and Intermittent Phentermine Therapy on Body Weight0Time (weeks)82428Munro JF et al. Brit Med J 1:352, 1968Weight Loss (lbs)36412162032Alternate Phentermine and DummyContinuousPhentermineContinuous DummyOrlistat Prevents Fat Digestion and Absorption Orlistat Prevents Fat Digestion and Absorption by Binding to Gastrointestinal Lipasesby Binding to Gastrointestinal LipasesTG=triglyceride; MG=monoglyceride; FA=fatty acid.Mucosal CellMucosal CellIntestinal LumenIntestinal LumenOrlistatOrlistatTGTGLIPASELIPASELIPASELIPASELIPASELIPASEBile AcidsBile AcidsMicelleMicelleMGMGFAFAEffect of Orlistat Dose on Fecal Fat ExcretionZhi et al. Clin Pharmacol Ther 1994;56:82.Fecal Fat Excretion (% intake)Orlistat Daily Dose (mg)020040060080010001200Effect of Long-term Orlistat Therapy on Body Weight0Weeks52Torgenson et al. Diabetes Care 2004;27:155Change in Weight (kg)104156208P0.001 vs placebo-4.1 kg-6.9 kgPlaceboOrlistatMeta-analysis of RCTs Evaluating Effect of Orlistat Therapy on Weight Loss at 1-YearStudy or Sub-categoryWMD (random)95% CIHollander 1998*Sjostrom 1998Davidson 1999Finer 2000Heuptman 2000Lindgarde 2000Rossner 2000Bakris 2002Broom 2002Kelley 2002*Miles 2002* Total (95% CI)Padwal et al. Int J Obes 2003;27:1437*All subjects had type 2 diabetesWMD=weighted mean differenceFavoursTreatmentFavoursControl-10-50105Independent Effect of Orlistat on Plasma LDL-CholesterolWeight Loss Category (%initial body weight)Change inPlasmaLDL-CholesterolConcentration(mmol/L)Segal et al. FASEB J. 1999;13:A873.*P 15PlaceboOrlistat*Orlistat Inhibits Dietary Cholesterol AbsorptionCholesterol Absorbed (% ingested)*P5% weight loss.Body Weight (lb.)Month206410814121816202224PlaceboSibutramine 10-20 mg/dWeight MaintenanceUse of Sibutramine within a Health Maintenance Use of Sibutramine within a Health Maintenance Organization Enhances Weight LossOrganization Enhances Weight Loss0WeeksPorter et al. Am J Manag Care 2004;10:369Weight Change (kg)2652No drug therapySibutramine therapyMeta-analysis of RCTs Evaluating Effect of Meta-analysis of RCTs Evaluating Effect of Sibutramine Therapy on Weight Loss at 1-YearSibutramine Therapy on Weight Loss at 1-YearStudy or Sub-categoryWMD (random)95% CIMcMahon 2000Smith 2001McMahon 2002 * Total (95% CI)Padwal et al. Int J Obes 2003;27:1437All subjects had hypertensionWMD=weighted mean difference-10FavoursTreatmentFavoursControl-50105Adverse Effects of Sibutramine Therapy Subjects (%)Adverse Effect Placebo SibutramineHeadache18.630.3Dry mouth4.217.2Constipation6.011.5Insomnia4.510.7Dizziness3.47.0Hypertension0.92.1Tachycardia0.62.6Palpitation0.82.0Meridia Package Insert, 2001.Blood Pressure and Pulse Rate After 1 Year Blood Pressure and Pulse Rate After 1 Year Sibutramine Therapy in Patients with Controlled Sibutramine Therapy in Patients with Controlled HypertensionHypertensionPlaceboSibutramineSystolic BP change(mm Hg)+1.5+2.7Diastolic BP change(mm Hg)-1.3+2.0 *Pulse rate change(beats/min)0 4.9 *Withdrawal due tohypertension (% subjects)1.45.3McMahon et al. Arch Intern Med 2000;160:2185.*P0.05 vs placebo.Additive Effects of Behavior and Diet Therapy with Additive Effects of Behavior and Diet Therapy with Pharmacotherapy for ObesityPharmacotherapy for ObesityWeight Change (%)Wadden et al. Arch Intern Med 2001;161:218.*P0.05 vs medication alone.Time (months)024812106Medication aloneMedication and behaviormodificationMedication, behaviormodification and meal replacements*