Pharmacological Treatments for Obesity and Weight Loss

Study Questions:

What is the comparative effectiveness of pharmacologic treatments for weight loss?


This was a systematic review and network meta-analysis of randomized clinical trials conducted among adults who were overweight or obese. Studies that examined five drugs approved by the US Food and Drug Administration for long-term weight loss with at least a 1-year follow-up were included. The drugs were orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide. Comparator groups could include another active agent or placebo. Studies were identified through searches of MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016, as well as clinical trial registries. The primary outcomes of interest included the proportion of patients with ≥5% weight loss, proportion with ≥10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year.


A total of 28 trials were identified. Participants (n = 29,018) were 74% women, median age 46 years, median baseline body weight 100.5 kg, and median baseline body mass index (BMI) was 36.1 kg/m2. A median 23% of placebo participants had ≥5% weight loss versus 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; surface under the cumulative ranking [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, with the most weight loss observed for phentermine-topiramate, 8.8 kg (95% CrI, −10.20 to −7.42 kg), followed by 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%) were observed in all the trials.


The investigators concluded that among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving ≥5% weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving ≥5% weight loss.


This systematic review/meta-analysis provides important information, which clinicians can discuss with patients who are considering using these agents to promote weight loss.

Clinical Topics: Prevention

Keywords: Benzazepines, Body Mass Index, Bupropion, Naltrexone, Obesity, Overweight, Pharmaceutical Preparations, Phentermine, Primary Prevention, Weight Loss

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