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    Original Investigation
    June 14, 2016

    Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis

    Author Affiliations
    • 1Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City
    • 2Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota
    • 3Division of Preventive Medicine, Mayo Clinic, Rochester, Minnesota
    • 4Division of Gastroenterology and Liver Diseases, Case Western Reserve University, Cleveland, Ohio
    • 5Division of Gastroenterology, University of California, San Diego, La Jolla
    • 6Department of Library Services, Mayo Clinic, Rochester, Minnesota
    • 7Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota
    • 8Division of Biomedical Informatics, University of California, San Diego, La Jolla
    JAMA. 2016;315(22):2424-2434. doi:10.1001/jama.2016.7602

    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.