Effect of Medications for Type 2 Diabetes on Cardiovascular Events and Mortality: A Comprehensive Pairwise and Network Meta-Analysis
- Journal
- Diabetes, obesity & metabolism (Q1)
- Published
- 30 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Giovanni Antonio Silverii, Valerio Velardi, Christian Marinelli, Antonino Lax, Matteo Monami, Edoardo Mannucci
- PMID
- 42530338
- DOI
- 10.1111/dom.71128
Why clinicians should know about it
- Picked for Epidemiology (top studies of the week, 2 August 2026).
- Picked for Internal Medicine (top studies of the week, 2 August 2026): T2DM meds impact on cardiovascular outcomes
- Picked for Endocrinology, Diabetes and Metabolism (top studies of the week, 2 August 2026).
Abstract
AIM: To assess the effect of all the approved classes of medications for type 2 diabetes on Major Adverse Cardiovascular events (MACE) and all-cause mortality. METHODS: We performed a pairwise and network meta-analysis, including randomised controlled trials with a duration of at least 40 weeks, comparing medications versus placebo or an active comparator, in which MACE and deaths were adjudicated. RESULTS: We included 93 studies. In pairwise meta-analyses, versus all comparators, GLP-1 receptor agonists (GLP1RA), SGLT-2 inhibitors (SGLT2i), metformin and pioglitazone were associated with a significant reduction of MACE and sulfonylureas with increased MACE. Furthermore, tirzepatide, SGLT2i and GLP1RA were associated with a significantly reduced all-cause mortality. In the principal (frequentist) network meta-analysis, metformin (OR 0.69, 95% CI 0.53-0.89), SGLT2i (0.82, 0.75-0.90), GLP1RA (0.87, 0.83-0.92) and tirzepatide (0.82, 0.72-0.93) were associated with a significant reduction of MACE versus placebo; no effect was observed for insulin, DPP4 inhibitors (DPP4i) or sulfonylureas. Tirzepatide (0.72, 0.64-0.82), SGLT2i (0.85, 0.80-0.91) and GLP1RA (0.85, 0.80-0.91) were associated with a significantly reduced mortality versus placebo; no effect was detected for other drugs. The sensitivity (Bayesian) analysis did not confirm the significance of results for pioglitazone on MACE. The certainty of evidence was moderate-to-high for GLP1RA, SGLT2i, Tirzepatide, DPP4i; low for metformin; low-to-moderate for other drugs. 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.