The Impact of GLP-1-Based Therapies on Cardiovascular Outcomes in Type 2 Diabetes: A Comprehensive Systematic Review and Network Meta-Analysis

GLP-1-based therapies were associated with a favourable cardiovascular profile in adults with type 2 diabetes, reducing all-cause mortality, cardiovascular mortality and major adverse cardiovascular events versus placebo in pooled analyses. A network meta-analysis of 15 trials provided agent-level estimates, with efpeglenatide, albiglutide and injectable semaglutide showing the most favourable MACE profiles, although many between-agent differences were not statistically significant.

Systematic review — Systematic review and network meta-analysis. Population: Adults with type 2 diabetes mellitus (T2DM) enrolled in randomized controlled trials. Sample size: 97,173 participants. Interventions: GLP-1-based therapies (tirzepatide, semaglutide, efpeglenatide, albiglutide). Cited by 1 other paper.

Fifteen trials involving 97,173 participants were included. Pairwise placebo-controlled analyses showed that GLP-1-based therapies significantly reduced all-cause mortality, cardiovascular mortality and MACE. In the NMA, mortality estimates for several agents favoured benefit, although most comparisons were not statistically significant. For MACE, efpeglenatide, albiglutide and injectable semaglutide showed the most favourable comparative profiles. Albiglutide reduced non-fatal MI versus placebo, whereas non-fatal stroke estimates were imprecise.

Researchers working on tirzepatide or semaglutide would use this paper as agent-level comparative evidence on cardiovascular outcomes in type 2 diabetes, complementing placebo-controlled trial data. It does not establish which agent is definitively best overall, because many network meta-analysis comparisons were not statistically significant and stroke estimates were imprecise. It also does not provide dosing or treatment-duration information.

Key findings

Fifteen trials involving 97,173 participants were included.
In pairwise placebo-controlled analyses, GLP-1-based therapies significantly reduced all-cause mortality, cardiovascular mortality and MACE.
In the network meta-analysis, efpeglenatide, albiglutide and injectable semaglutide showed the most favourable comparative profiles for MACE.
Albiglutide reduced non-fatal myocardial infarction versus placebo.
Non-fatal stroke estimates were imprecise.
Most between-agent mortality comparisons were not statistically significant.

Limitations

Most between-agent mortality comparisons were not statistically significant, so agent-level claims are limited.
Non-fatal stroke estimates were imprecise.
Network meta-analysis relies on indirect comparisons across trials, which may introduce heterogeneity.
Treatment duration and doses were not reported in the abstract, limiting direct clinical interpretation.

The record

Journal: Diabetes, obesity & metabolism 28(8): 7137-7148
Published: 2026-05-31
PMID: 42219271 — DOI: 10.1111/dom.70915
MeSH terms: Humans, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Hypoglycemic Agents, Treatment Outcome, Glucagon-Like Peptide 1, Randomized Controlled Trials as Topic, Tirzepatide, Semaglutide
Author countries: Taiwan

Peptide profiles: Tirzepatide, Semaglutide.

All indexed evidence: Tirzepatide trials & papers, Semaglutide trials & papers.