Core Viewpoint - The article discusses a systematic review and network meta-analysis published in The Lancet, which evaluates the effectiveness and safety of seven weight loss medications for overweight and obese adults, highlighting that the combination of phentermine-topiramate and GLP-1 receptor agonists, particularly semaglutide, show the most significant weight loss effects [5][19]. Research Methodology - The research team systematically searched three major databases: PubMed, Embase, and Cochrane Library, including randomized controlled trials (RCTs) published until March 23, 2021, focusing on weight loss medications for overweight and obese adults [7]. - Exclusion criteria included studies with a crossover design, combination of multiple medications, participants with psychological disorders, pregnant women, normal weight individuals, and non-English publications [7]. Study Results - A total of 14,605 articles were screened, resulting in 132 studies included, with 48,209 participants. The median age of participants was 47 years, with a female proportion of 76% and a median BMI of 35.3 kg/m² [11]. - The study assessed the impact of seven medications on six outcome measures, including weight loss percentage, proportion of participants achieving 5% or 10% weight loss, quality of life improvement, reduction in depressive symptoms, and safety indicators [10]. Comparative Effectiveness - Compared to lifestyle modifications alone, all weight loss medications resulted in additional weight loss. Phentermine-topiramate showed the most significant weight loss effect, with an odds ratio (OR) of 8.02 for achieving a weight reduction of ≥5% and an average weight loss percentage of -7.98% [17]. - GLP-1 receptor agonists also demonstrated significant effects, with an OR of 6.33 for achieving a weight reduction of ≥5% and an average weight loss percentage of -5.79% [17]. Specific Drug Analysis - Among GLP-1 receptor agonists, semaglutide exhibited the most pronounced weight loss effects, with an OR of 9.82 for achieving a weight reduction of ≥5% and an average weight loss percentage of -11.40% [18]. - Safety data indicated that medications like naltrexone-bupropion, phentermine-topiramate, GLP-1 receptor agonists, and orlistat were associated with an increased risk of discontinuation due to adverse events [18]. Conclusion - The network meta-analysis provides high to moderate confidence evidence that phentermine-topiramate and GLP-1 receptor agonists, especially semaglutide, are the most effective weight loss medications, with average weight reductions ranging from 6% to 11% [19].