MA: Several drugs are effective for weight loss in obese or overweight adults; it's unclear whether they improve health outcomes

Reference

Shi Q, Wang Y, Hao Q, et al. Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials. Lancet 2022;399(10321):259-269.

Synopsis

These authors searched PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov to identify randomized trials of various medications to promote weight loss in overweight or obese adults. The included trials did not have to include persons with comorbid conditions but had to compare a medication with lifestyle modification with or without a placebo. The studies had to report weight loss–related data and quality of life but did not have to report other health outcomes (eg, gastrointestinal symptoms, body image, changes in blood pressure, or changes in laboratory parameters such as glycated hemoglobin and lipid levels). The authors also accepted data that were not necessarily analyzed by intention to treat. Ultimately, they included 143 unique trials with 49,810 participants, 75% of whom were women. The median length of the trials was 24 weeks. The authors identified a high risk of bias due to protocol deviations and missing outcome data, and they had concerns about how adverse events were assessed. Nonetheless, they decided they had passed the point of no return and performed a network meta-analysis. After a bunch of statistical gymnastics, they found that phentermine-topiramate was the most effective medication in achieving at least a 5% weight loss (odds ratio [OR] = 8.02; 95% CI 5.24 - 12.27), followed by glucagon-like peptide 1 (GLP-1) receptor agonists (OR = 6.33; 5 - 8). The order of effectiveness in achieving at least a 10% weight loss was the same. Although effective in achieving weight loss, most drugs also had significant discontinuation due to adverse events: naltrexone-bupropion (OR = 2.69; 2.11 - 3.43), phentermine-topiramate (OR = 2.40; 1.69 - 3.42), GLP-1 receptor agonists (OR = 2.17; 1.71 - 2.77), and orlistat (OR = 1.72; 1.44 - 2.05). Quality-of-life scores improved to a greater degree for phentermine-topiramate (standardized mean difference [SMD] 0.42), followed by naltrexone-bupropion (SMD 0.36), and GLP-1 receptor agonists (SMD 0.29). The authors report that, compared with lifestyle modification, medications caused greater degrees of lower glycated hemoglobin and lipid levels but not systolic blood pressure. For most of the data, the authors report significant heterogeneity. Finally, they do not report on other important outcomes, such as mortality, cardiac events, development or regression of diabetes, and so forth.