Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta analysis.
IMPORTANCE Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. OBJECTIVE To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta analysis. DATA SOURCES MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries. STUDY SELECTION Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration approved long term weight loss agents (orlistat, lorcaserin, naltrexone bupropion, phentermine topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo. DATA EXTRACTION AND SYNTHESIS Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria. MAIN OUTCOMES AND MEASURES Proportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year. RESULTS Twenty eight randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5% weight loss vs 75% of participants taking phentermine topiramate (odds ratio [OR] 9.22; 95% credible interval [CrI] 6.63 12.85; SUCRA, 0.95) 63% of participants taking liraglutide (OR, 5.54; 95% CrI, 4.16 7.78; SUCRA, 0.83) 55% taking naltrexone bupropion (OR, 3.96; 95% CrI, 3.03 5.11; SUCRA, 0.60) 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38 4.05; SUCRA, 0.39) and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34 3.09; SUCRA, 0.22) All active agents were associated with significant excess weight loss compared with placebo at 1 year phentermine topiramate, 8.8 kg (95% CrI, 10.20 to 7.42 kg) liraglutide, 5.3 kg (95% CrI, 6.06 to 4.52 kg) naltrexone bupropion, 5.0 kg (95% CrI, 5.94 to 3.96 kg) lorcaserin, 3.2 kg (95% CrI, 3.97 to 2.46 kg) and orlistat, 2.6 kg (95% CrI, 3.04 to 2.16 kg) Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11 4.23) and naltrexone bupropion (OR, 2.64; 95% CrI, 2.10 3.35) were associated with the highest odds of adverse event related treatment discontinuation. High attrition rates (30% 45% in all trials) were associated with lower confidence in estimates. CONCLUSIONS AND RELEVANCE Among overweight or obese adults, orlistat, lorcaserin, naltrexone bupropion, phentermine topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5% weight loss at 52 weeks. Phentermine topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss.
JAMA