Bariatric treatments for adult obesity - Institute of Health Economics

PharmacotherapyDescription of the included studiesOne Cochrane systematic review and meta-analysis 20 assessed 30 double-blind, placebo-controlledtrials (16 trials on orlistat, 10 on sibutramine, and four on rimonabant). Twenty-seven RCTs (16 onorlistat, seven on sibutramine, and four on rimonabant) were weight loss trials, in which antiobesitymedications were used in conjunction with a weight loss diet for 1 to 4 years. Four orlistat weightloss trials and one rimonabant weight loss trial also contained a secondary weight maintenance year.The remaining three sibutramine trials were weight maintenance studies with follow-up periods of 1and 1.5 years from the point of randomization. Because another review 59 focused on discontinuationrates of antiobesity drugs and the other review 60 only included 29 RCTs on orlistat, the followingsection will present information mainly from the Cochrane review. 20Methodological quality and limitationsEligibility criteria were reported in all 30 studies. In all studies, co-interventions appeared to beequally applied to intervention and control arms. No details about double-blinding were provided inany study. Blinding of outcome assessors was not specified in any study.The major methodological limitation was high attrition rates. The average attrition rate of the 16studies on orlistat was about 30%, with rates ranging from 0% to 66%. In XENDOS (Xenical in thePrevention of Diabetes in Obese Subjects), the largest and longest orlistat trial, approximately 66%of patients dropped out over the 4-year follow-up period. The average attrition rate for studies onsibutramine was about 40%, with rates ranging from 11% to 51%. The average of attrition rate forstudies on rimonabant was also about 40%, with rates ranging from 32% to 49%.High attrition rates in both treatment and control groups compromised the internal validity ofpharmacotherapy studies. Investigators attempted to address this limitation by using a lastobservation-carried-forwardanalysis, which can bias results in either direction depending on thedifferential dropout rates in the treatment and control arms and the reasons for withdrawal. It isdifficult to compensate for such high attrition rates by using any form of analysis.EffectsMeta-analysis of RCTs that used orlistat, sibutramine, or rimonabant demonstrated that each drugresulted in average placebo-subtracted weight reductions of approximately 5 kilograms or less.Weight maintenance studies for each drug reported similar amounts of weight regain in both themedication treatment and the placebo study arms; therefore, the original difference in weight lossbetween groups was maintained.Studies that enrolled patients with diabetes reported slightly smaller losses of weight with orlistat orrimonabant therapy, but this finding was not observed with sibutramine therapy.Since no head-to-head comparison studies of the three drugs were assessed in the includedsystematic reviews/HTAs, the comparative effectiveness of the three drugs (and particularly oforlistat and sibutramine) remains to be determined.Bariatric treatments for adult obesity 83