Relative Efficacy of Next‐Generation Incretin Therapies for Cardio‐Renal Protection in Type 2 Diabetes: Evidence From a Network Meta‐Analysis
Authors' conclusion
Cardiovascular and renal benefits of GLP-1-based therapies are outcome-specific. Semaglutide favoured MACE/MI reduction, dulaglutide and tirzepatide supported stroke prevention, and albuminuria outcomes were more responsive than eGFR. Further long-term head-to-head trials are needed.
Study context
- Population
- High-risk T2D populations; RCTs published 2014–2025 with ≥ 6 months follow-up34 trials
- Comparison
- Modern GLP-1 RAs, tirzepatide and cotadutide vs placebo
- Outcome
- Cardiovascular and renal outcomes
Methodological detailsrandom- and common-effects models, p-score rankings
- Random- and common-effects models
- P-score rankings
Pooled result
As reported in the abstract
- Semaglutide regimens showed the most consistent reduction in major adverse cardiovascular events (MACE) and myocardial infarction (MI) vs placebo; strongest effect with semaglutide plus SGLT2 inhibition
- Dulaglutide 1.5 mg and tirzepatide 15 mg significantly reduced stroke risk
- Cardiovascular death estimates largely imprecise, with evidence of small-study effects
- eGFR changes generally modest
- Marked UACR reductions, particularly with dulaglutide plus dapagliflozin, DPP-4 inhibitors and semaglutide 1 mg
Further pooled results
Principal component analysis (PCA) of clinical variables
- PCA confirmed strong cardiometabolic-renal interdependence
Original publication
Relative Efficacy of Next‐Generation Incretin Therapies for Cardio‐Renal Protection in Type 2 Diabetes: Evidence From a Network Meta‐Analysis. Diabetes Obes Metab. Published 10 March 2026. doi:10.
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