Glucagon-like peptide-1 receptor agonists for primary cardiovascular disease prevention in type 2 diabetes, a systematic review
In brief
GLP-1 agonists fail to lower major cardiovascular events in primary-prevention diabetes
A systematic review of 11 industry-funded trials involving 77 419 type-2 diabetics found no significant reduction in major adverse cardiovascular events among the 16 672 participants without prior cardiovascular disease (hazard ratio 0.88, not statistically significant). Evidence quality was low, highlighting the need for dedicated trials before recommending GLP-1 drugs for primary prevention.
- Journal
- BMJ open diabetes research & care (Q1)
- Published
- 19 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Guillaume Grenet, Raha Eskandari, Joyce Ko, Stephen P Adams, Douglas M Salzwedel, Balraj S Heran, et al.
- PMID
- 42618306
- DOI
- 10.1136/bmjdrc-2026-006225
Why clinicians should know about it
- Picked for Bariatric and Metabolic Surgery (top studies of the week, 23 August 2026): Systematic review of GLP‑1 CV prevention, not surgical
- Picked for Nephrology (top studies of the week, 23 August 2026): GLP‑1 RAs primary CV prevention
Abstract
We aimed to estimate the cardiovascular (CV) benefit of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) without a history of CV disease (CVD) (primary CVD prevention). We searched MEDLINE and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) and Epistemonikos for systematic reviews (up to July 4, 2025). We included RCTs of patients with T2D comparing a GLP-1 RA to placebo using a CV or renal primary outcome. 11 drug manufacturer-funded trials (77 419 participants) were included. We used version 1 of the Cochrane risk of bias tool. Our primary analysis was the pooled estimate of the treatment effect in primary CVD prevention. Outcomes of interest were major adverse cardiovascular events (MACE, primary outcome), all-cause mortality, CV mortality, myocardial infarction, stroke, and serious adverse events (secondary outcomes). Only 26% of participants were primary CVD prevention patients. The pooled estimates of treatment effect for primary CVD prevention were not significant for the primary outcome, MACE (pooled HR 0.88, 95% CI 0.74 to 1.05, based on eight trials, n=16 672), and all secondary outcomes. The certainty of the evidence was rated as low due to trials' risk of bias and imprecision. Our review was limited to subgroup analyses of aggregated data from studies not powered for primary prevention alone. Current evidence is insufficient to establish CV benefits of GLP-1 RAs in T2D without a history of CVD, and dedicated primary prevention trials are needed.
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.