Efficacy and safety of GLP-1RAs for people with obesity: A systematic review based on RCT and Bayesian network meta-analysis

Background: GLP-1 receptor agonists (GLP-1RAs) reduce glucagon and glycogen secretion, inhibit appetite and slow gastric empties and have recently been approved to treat obesity. Objective: To explore the safety and efficacy of GLP-1RAs in the treatment of obesity and clarify the optimal GLP1RAs treatment regimen. Methods: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for English randomized controlled trials (RCTs) on GLP-1RAs in the treatment and management of obesity published before July 18, 2023. Literature screening and data extraction were performed independently by three researchers. Bayesian random effect model was used to compare the effects of interventions. Continuous variables were expressed as mean difference with 95% CI, and dichotomous variables were reported as RR with 95% CI. Results: A total of 29 studies with 10,333 participants were included in the present study. The combination of cagrilintide and semaglutide (short for cagrANDsema) was an optimal strategy for weight loss and glycosylated hemoglobin (HbA1c) reduction. Compared to placebo, cagrANDsema reduced weight by - 14.13 kg (95% CI: -16.49, -11.73) and HbA1c by - 0.33% (95% CI: -0.41, -0.25). Moreover, this study indicated that orforglipron and semaglutide also had relatively good effects on weight loss. Meta-regression results indicated that higher dose levels might have better effects on weight loss. Conclusions: CagrANDsema exerts the best effect for weight loss. In terms of current dose levels, a higher dose gets better weight-loss effects without increasing the risk of adverse events.