Tirzepatide demonstrated the largest reductions in HbA1c, body weight, and systolic blood pressure among once-weekly GLP-1RAs. The analysis, published in Diabetes Research and Clinical Practice, evaluated glycemic efficacy, tolerability, and safety using a Bayesian network meta-analytic approach.

The synthesis included studies from PubMed, Embase, and the Cochrane Central Register through June 2024. Outcomes assessed included HbA1c change, weight loss, systolic blood pressure change, gastrointestinal adverse events, and discontinuation. All GLP-1RAs reduced HbA1c versus placebo, ranging from −0.66% with dulaglutide 1.5 mg to −1.4% with tirzepatide 15 mg. Tirzepatide also produced the greatest weight loss (−8.7 kg) and systolic blood pressure reduction (−4.8 mmHg) but had higher nausea (OR 6.4) and diarrhea risks (OR 3.5).

Polyethylene glycol loxenatide 100 μg provided effective glycemic control with the lowest rates of gastrointestinal adverse events and treatment discontinuation.