Efficacy of Weight‐Lowering Agents on Fat Distribution: A Systematic Review and Network Meta‐Analysis of Randomized Controlled Trials

BACKGROUND: Pharmacotherapy offers a potential solution for individuals with overweight and obesity to decrease their body weight. However, there is limited knowledge of the effects of antiobesity agents on the distribution of body fat. METHODS: The PubMed, Embase, and Cochrane Library databases were reviewed for randomized controlled trials (RCTs) of weight-lowering drugs between inception and May 23, 2023. The main results were visceral and subcutaneous adipose tissue (VAT and SAT). Secondary outcomes were altered body weights and waist circumferences. For the statistical analysis, STATA 14.0 was utilized, and the frequentist method was used for random-effect network meta-analyses. RESULTS: A total of 39 articles including 41 RCTs with 2741 patients were included. GLP-1 receptor agonists and SGLT-2 inhibitors were observed to lower VAT (-0.90 [-1.32 to -0.47] and -0.66 [-1.22 to -0.10]) after a mean of 29.4 weeks, whereas only GLP-1 receptor agonists reduced SAT (-1.01 [-1.58 to -0.43]). Naltrexone-bupropion, GLP-1 receptor agonists, SGLT-2 inhibitors, and metformin were found to reduce body weight (-5.60 [-8.64 to -2.56] kg, -4.73 [-5.58 to -3.88] kg, -3.20 [-4.69 to -1.72] kg, and -1.93 [-3.01 to -0.85] kg). Lastly, waist circumference was decreased by GLP-1 receptor agonists, metformin, SGLT-2 inhibitors, and naltrexone-bupropion. CONCLUSION: This analysis demonstrated that GLP-1 receptor agonists may have advantages over other antiobesity agents in reducing VAT and SAT. SGLT-2 inhibitors were more helpful to reduce VAT. The clinical significance relates to physicians being able to choose appropriate weight-loss agents in accordance with a patient's fat distribution.