1.Network meta-analysis of the efficacy of GLP-1 receptor agonists in the treatment of type 2 diabetes mellitus complicated with obesity/overweight
Jin ZENG ; Juliang CHEN ; Ziwei HU ; Liangran YAO ; Yakun ZHAN
China Pharmacy 2026;37(10):1357-1363
OBJECTIVE To systematically evaluate the efficacy and safety of 6 kinds of GLP-1RAs in the treatment of type 2 diabetes mellitus (T2DM) patients with overweight or obesity, and to provide evidence-based reference for clinical practice. METHODS A comprehensive search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, CNKI, VIP, Wanfang Data, and CBM from the inception to December 1, 2025. Randomized controlled trials (RCTs) were screened according to inclusion and exclusion criteria. Data extraction and risk of bias assessment were performed on the included studies. Network meta-analysis was conducted using Stata 17.0 software. RESULTS A total of 29 eligible RCTs were included, involving 7 404 patients. Six GLP-1RAs were evaluated: semaglutide, liraglutide, exenatide, dulaglutide, polyethylene glycol loxenatide, and beinaglutide. In terms of glycemic control, semaglutide had the highest probability of ranking first in reducing glycated hemoglobin (HbA1c) and fasting plasma glucose levels, followed by polyethylene glycol loxenatide. In terms of weight management, semaglutide showed the highest probability of ranking first, followed by liraglutide and exenatide. Regarding safety, dulaglutide had the highest probability of ranking first in reducing the incidence of gastrointestinal adverse events; none of the GLP-1RAs significantly increased the risk of severe hypoglycemia. Subgroup analysis revealed that liraglutide 1.8 mg, qd and exenatide extend-release 2.0 mg, qw demonstrated superior efficacy in reducing HbA1c and body weight compared with other doses/dosage forms of the same agents. CONCLUSIONS For T2DM patients with overweight or obesity, semaglutide offers the greatest benefits in glycemic control and weight reduction, while dulaglutide demonstrates superior gastrointestinal tolerability. Liraglutide 1.8 mg, qd and exenatide extend-release 2.0 mg, qw show relatively better overall efficacy in glycemic control and weight reduction among the same agents.
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