Effect of Medications for Type 2 Diabetes on Cardiovascular Events and Mortality: A Comprehensive Pairwise and Network Meta‐Analysis
Authors' conclusion
SGLT2i, GLP1RA, tirzepatide and (with lower quality of evidence) pioglitazone and metformin are associated with a reduced incidence of cardiovascular events; tirzepatide, SGLT2i and GLP1RA are also associated with a reduced all-cause mortality.
Study context
- Population
- RCTs of approved T2D medications lasting ≥40 weeks with adjudicated Major Adverse Cardiovascular events (MACE) and deaths93 studies
- Comparison
- Approved classes of T2D medications vs placebo or active comparator
- Outcome
- MACE and all-cause mortality
Methodological detailspairwise and network meta-analysis, frequentist principal analysis, Bayesian sensitivity analysis, RCTs ≥40 weeks, adjudicated MACE and deaths
- Pairwise and network meta-analysis
- Frequentist principal analysis
- Bayesian sensitivity analysis
- RCTs ≥40 weeks
- Adjudicated MACE and deaths
Pooled result
As reported in the abstract
MACE vs placebo (principal frequentist network meta-analysis)
Each group vs placeboOdds ratio (95% CI)
Metformin
0.69(0.53–0.89)
SGLT2i
0.82(0.75–0.90)
GLP1RA
0.87(0.83–0.92)
Tirzepatide
0.82(0.72–0.93)
Further pooled results
| Outcome | OR (CI) | |
|---|---|---|
| All-cause mortality vs placebo (principal frequentist network meta-analysis)Tirzepatidevs Placebo | 0.72 (0.64–0.82) | |
| All-cause mortality vs placebo (principal frequentist network meta-analysis)SGLT2ivs Placebo | 0.85 (0.80–0.91) | |
| All-cause mortality vs placebo (principal frequentist network meta-analysis)GLP1RAvs Placebo | 0.85 (0.80–0.91) | |
| 0.512Odds ratio (log scale) |
All-cause mortality vs placebo (principal frequentist network meta-analysis)
- No effect on mortality detected for other drugs
Pairwise meta-analyses vs all comparators
- GLP1RA, SGLT2i, metformin and pioglitazone associated with significantly reduced MACE; sulfonylureas with increased MACE
- Tirzepatide, SGLT2i and GLP1RA associated with significantly reduced all-cause mortality
Sensitivity (Bayesian) analysis
- Did not confirm significance of pioglitazone on MACE
Certainty of evidence
- Moderate-to-high for GLP1RA, SGLT2i, tirzepatide, DPP4 inhibitors (DPP4i); low for metformin; low-to-moderate for other drugs
Original publication
Effect of Medications for Type 2 Diabetes on Cardiovascular Events and Mortality: A Comprehensive Pairwise and Network Meta‐Analysis. Diabetes Obes Metab. Published 30 July 2026. doi:10.
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