Efficacy and safety of different once-weekly glucagon-like peptide-1 receptor agonists-A systematic review and Bayesian network meta-analysis.

There are less comparisons among once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs),which is not conducive to refined clinical treatment. We searched in Pubmed, Embase, and Cochrane Central Register of Controlled Trials from database creation date to June 1, 2024. The primary glycemic efficacy was changes from baseline to endpoint for HbA1c. We performed Bayesian network meta-analysis calculating mean differences (MDs) for continuous outcomes and odds ratios (OR) for dichotomous outcomes. All once-weekly GLP-1RAs outperformed placebo in reducing HbA1c (MD: -0.66 % [-0.81 %, -0.5 %] for dulaglutide 1.5 mg to -1.4 % [-1.6 %, -1.2 %] for tirzepatide 15 mg). Tirzepatide 15 mg showed superior weight loss (MD: -8.7 [-10, -6.8]) and systolic blood pressure reduction (MD: -4.8 [-8.2, -1.4]) versus other GLP-1RAs, but higher nausea (OR: 6.4 [4.3, 9.6]) and diarrhea risks (OR: 3.5 [2.5, 5.2]). Polyethylene glycol loxenatide 100 μg provided effective glucose control with the lowest gastrointestinal and discontinuation risks. Tirzepatide demonstrates superior efficacy in glycemic control, weight reduction, and blood pressure reduction, yet is associated with high risk of adverse events. In contrast, polyethylene glycol loxenatide offers effective glycemic management with the lowest withdrawal probability. For patients with Type 2 diabetes mellitus and cardiovascular disease, dulaglutide is preferable.