Association of long-term weight management pharmacotherapy with multiple health outcomes: an umbrella review and evidence map

Abstract

Multiple meta-analyses (MAs) have demonstrated that six pharmacotherapies, including orlistat, liraglutide, phentermine/topiramate, naltrexone/bupropion, semaglutide, and tirzepatide, improve weight loss and weight maintenance. However, few studies have synthesized and evaluated the quality of this evidence. To identify the relevant MAs of randomized clinical trials (RCTs) that explored the association between the six pharmacotherapies and obesity-related health outcomes and adverse events (AEs). A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Web of Science from database inception up to January 2024. We calculated the effect size as the mean difference and risk ratio using the random-effects model. The quality of MAs was evaluated using “A Measurement Tool to Assess Systematic Reviews 2”. Sixteen MAs comprising 235 RCTs that described 115 unique associations between the six pharmacotherapies and various health outcomes were included. Overall, 101 statistically significant associations (88%) had beneficial outcomes on body weight, weight loss, waist circumference, body mass index, total cholesterol, triglycerides, both low-density and high-density lipoprotein cholesterol, blood pressure, and glycemic profile. The pharmacotherapies were associated with significant weight loss and partial improvements in the lipid profile, blood pressure, and glycemic control among individuals with overweight or obesity. Notable AEs were associated with liraglutide, naltrexone/bupropion, semaglutide, and orlistat. The methodological quality of the included MAs requires improvement. This umbrella review identified significant beneficial associations between pharmacotherapies and anthropometric measures, lipid profile, blood pressure, glycemic profile, and quality-of-life outcomes in individuals with overweight or obesity. In addition, the umbrella review highlighted safety considerations. The findings affirm the efficacy of the six pharmacotherapies in promoting weight loss in this demographic. Further clinical trials with long-term follow-up are essential to evaluate the effects of these pharmacotherapies on clinical outcomes, including cancer, cardiovascular events, and mortality.