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

• Published in: Biomedicine & pharmacotherapy Vol. 171; p. 116150
• Main Authors: Li, Hong, Yu, Guanzheng, Huang, Qi, Yang, Bao, Nie, Juan, Liu, Yinbei, Tu, Xing
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.02.2024; Elsevier
• Subjects: Bayesian network meta-analysis; Diabetes Mellitus, Type 2 - drug therapy; GLP-1RAs; Glycated Hemoglobin; Humans; Hypoglycemic Agents - therapeutic use; Network Meta-Analysis; Obesity; Obesity - drug therapy; Overweight; Randomized Controlled Trials as Topic; RCT; Weight Loss; Obesity; RCT; Bayesian network meta-analysis; GLP-1RAs; Overweight
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2024.116150

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. To explore the safety and efficacy of GLP-1RAs in the treatment of obesity and clarify the optimal GLP-1RAs treatment regimen. 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. 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. 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. [Display omitted] •GLP-1 receptor agonists (GLP-1RAs) such as cagrilintide and semaglutide are effective in reducing weight and glycosylated hemoglobin (HbA1c) levels in individuals with obesity.•The combination of cagrilintide and semaglutide (cagrANDsema) shows the best effect for weight loss, reducing weight by an average of 14.13 kg.•In addition to cagrANDsema, orforglipron and semaglutide also have positive effects on weight loss.•A higher dose of GLP-1RAs may lead to better weight-loss effects, without significantly increasing the risk of adverse events.•GLP-1RAs offer a promising treatment option for obesity, providing both safety and efficacy.