Efficacy and safety of different once-weekly glucagon-like peptide-1 receptor agonists—A systematic review and Bayesian network meta-analysis
Authors' conclusion
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.
Study context
- Population
- Trials of once-weekly GLP-1 RAs; PubMed, Embase and Cochrane CENTRAL searched to June 1, 2024
- Comparison
- Once-weekly GLP-1 RAs vs placebo and each other
- Outcome
- Change in HbA1c from baseline to endpoint
Pooled result
As reported in the abstract
Change in HbA1c
Each group vs placeboMD, % (CI)
Dulaglutide 1.5 mgsmallest reduction among once-weekly GLP-1 RAs
−0.66(−0.81 %, −0.5 %)
Tirzepatide 15 mglargest reduction among once-weekly GLP-1 RAs
−1.4(−1.6 %, −1.2 %)
Further pooled results
| Outcome | MD (CI) | |
|---|---|---|
| Weight lossTirzepatide 15 mgvs Other GLP-1 RAs | −8.7 (−10 to −6.8) | |
| Systolic blood pressure reductionTirzepatide 15 mgvs Other GLP-1 RAs | −4.8 (−8.2 to −1.4) | |
| −15−10−505Difference (linear scale) |
Glucose control with polyethylene glycol loxenatide 100 μg
- Polyethylene glycol loxenatide 100 μg provided effective glucose control
Safety
| Outcome | OR (CI) | |
|---|---|---|
| NauseaTirzepatide 15 mgvs Other GLP-1 RAsHigher risk with tirzepatide 15 mg | 6.4 (4.3–9.6) | |
| DiarrheaTirzepatide 15 mgvs Other GLP-1 RAsHigher risk with tirzepatide 15 mg | 3.5 (2.5–5.2) | |
| 0.10.31310Odds ratio (log scale) |
Gastrointestinal and discontinuation risks
- Polyethylene glycol loxenatide 100 μg had the lowest gastrointestinal and discontinuation risks
Original publication
Efficacy and safety of different once-weekly glucagon-like peptide-1 receptor agonists—A systematic review and Bayesian network meta-analysis. Diabetes Res Clin Pract. Published 24 October 2025. doi:10.
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