Network meta-analysis ranks once-weekly GLP-1 agonists by efficacy and tolerability

This Bayesian network meta-analysis positions tirzepatide, semaglutide, dulaglutide, and polyethylene glycol loxenatide against each other across 20 efficacy and safety outcomes to inform tailored once-weekly incretin selection in Type 2 diabetes mellitus (T2DM).

📅 Journal publication: Dec 2025 (online Oct 24, 2025) · Last updated: Oct 12, 2026

tirzepatidesemaglutidedulaglutideexenatidepolyethylene glycol loxenatideGLP-1 receptor agonistsGIP/GLP-1 agonistType 2 diabetesnetwork meta-analysisHbA1cweight lossgastrointestinal adverse events Endocrinology / Diabetes / Obesity

Background Information

Tirzepatide outshines in efficacy but watch for side effects.

Understanding the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) can improve tailored clinical treatment for Type 2 diabetes mellitus. Tirzepatide 15 mg showed the greatest reduction in hemoglobin A1c (HbA1c), weight, and blood pressure but had higher nausea and diarrhea risk. Polyethylene glycol loxenatide 100 μg had lower gastrointestinal side effects. Tirzepatide provides strong glycemic and weight benefits with notable adverse effects, while polyethylene glycol loxenatide offers a more tolerable profile. Dulaglutide is suitable for patients with cardiovascular disease. Tirzepatide excels in efficacy but poses higher adverse event risks; loxenatide balances efficacy and tolerability.

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Authors: Xu Y, Ji G, Shi C, Tan Y, Wang L, Gui Y

Citation: Xu Y, Ji G, Shi C, et al. Efficacy and safety of different once-weekly glucagon-like peptide-1 receptor agonists-A systematic review and Bayesian network meta-analysis. Diabetes research and clinical practice. 2025;230:112954. doi:10.1016/j.diabres.2025.112954

Article Links: PubMed · Journal / DOI

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Executive Summary

Study Design

Patient Population

Primary Outcomes

Secondary Outcomes & Safety Profile

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Clinical Pearls

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