Dose-Response Relationship of Glucagon-like Peptide-1 Receptor Agonists on HbA1c and Body Weight in Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-Analysis

Objective: To explore the dose-response relationship of GLP-1 RAs in reducing glycated hemoglobin (HbA1c), body weight, and incidence of adverse events among type 2 diabetes mellitus (T2DM) patients.

Methods: This systematic review and network meta-analysis followed the PRISMA guidelines. We conducted a systematic search of PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and Web of Science for articles published up to October 20, 2024. Selected studies were randomized controlled trials focusing on adult T2DM patients treated with GLP-1 RAs. Primary outcomes included changes in HbA1c, body weight, and incidence of adverse events. Data extraction was performed by 2 independent researchers. Model-Based Network Meta-Analysis employing a random-effects Bayesian approach was used to synthesize the data.

Results: The analysis included 62 trials with 17 140 participants. The study revealed a nonlinear dose-response relationship for various GLP-1 RAs, indicating significant reductions in HbA1c and body weight. Tirzepatide (10 mg/wk) was found to be particularly effective, reducing HbA1c by -1.76% (95% credible intervals: -2.10 to -1.41) and body weight by -8.63 kg (95% credible intervals: -9.84 to -7.39) without a significant increase in adverse events, highlighting its optimal balance between efficacy and safety. Other GLP-1 RAs also showed significant efficacy, underscoring the overall benefits of this class of medications in managing T2DM.

Conclusion: Our findings indicate a nonlinear dose-response relationship for GLP-1 RAs in managing T2DM. Tirzepatide at a dose of 10 mg/wk is identified as an optimal clinical dose offering a balance between efficacy and safety, contributing to refining T2DM management strategies and potentially enhancing patient outcomes.