Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials
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Aims: Glucose-lowering, glucagon-like peptide-1 (GLP-1) receptor agonists reduce incidence of major cardiovascular (CV) events in patients with Type 2 diabetes mellitus (DM). However, randomized clinical trials reported inconsistent effects on myocardial infarction (MI) and stroke, and limited data in DM patients without established CV disease (CVD). Very recently, new relevant evidence was available from additional CV outcome trials (CVOTs) that also included large subgroups of patients with DM without established CVD. Thus, the aim of this meta-analysis was to investigate the effects of GLP-1 receptor agonists on major CV events and safety in DM patients with and without established CVD. Methods and results: In this trial-level meta-analysis, we analysed data from randomized placebo-controlled CVOTs assessing efficacy and safety of GLP-1 receptor agonists in adult patients with Type 2 DM. We searched PubMed, Embase, Cochrane, ISI Web of Science, SCOPUS, and clinicaltrial.gov databases for eligible trials. Of 360 articles identified and screened for eligibility, seven CVOTs were included, with an overall of 56 004 patients included. The difference in efficacy with respect to the major adverse cardiovascular events (MACE) primary endpoint (including CV mortality, non-fatal MI, and non-fatal stroke) between patients with established CVD and patients with CV risk factors only was not significant [pooled interaction effect, expressed as ratio of hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.85–1.34]. In the analysis of the whole population of DM patients, GLP-1 receptor agonists showed a significant 12% reduction in the hazard of the three-point MACE composite endpoint (HR 0.88, 95% CI 0.80–0.96) and a significant reduction in the risk of CV mortality (HR 0.88, 95% CI 0.79–0.98), all-cause mortality (HR 0.89, 95% CI 0.81–0.97), fatal and non-fatal stroke (HR 0.84, 95% CI 0.76–0.94), and heart failure (HF) hospitalization (HR 0.92, 95% CI 0.86–0.97). No significant effect was observed for fatal and non-fatal MI (HR 0.91, 95% CI 0.82–1.02), although in a sensitivity analysis, based on a less conservative statistical approach, the pooled HR become statistically significant (HR 0.91, 95% CI 0.83–1.00; P = 0.039). No excess of hypoglycaemia, pancreatitis, and pancreatic cancer was observed between GLP-1 receptor agonists and placebo. Conclusion: Glucagon-like peptide-1 receptor agonists significantly reduce MACE, CV and total mortality stroke, and hospitalization for HF, with a trend for reduction of MI, in patients with Type 2 DM with and without established CVD.
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Recent systematic reviews and meta-analyses found that GLP-1R agonists reduced major adverse cardiovascular events in T2D patients and also had beneficial effects on kidney outcome.
“Recent systematic reviews and meta-analyses found that GLP-1R agonists reduced major adverse cardiovascular events in T2D patients280–282 and also had beneficial effects on kidney outcome.283”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [282]
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- Authors
- Marsico, F., Paolillo, S., Gargiulo, P., Bruzzese, D., Dell’Aversana, S., Esposito, I., Renga, F., Esposito, L., Marciano, C., Dellegrottaglie, S., Iesu, I., & Perrone Filardi, P.
- Affiliations
- University of Naples Federico II (IT)
- Clinica Mediterranea (IT)
- Istituto Diagnostico Varelli , Via Cornelia dei Gracchi, 65, I-80126 Naples, Italy
- Villa dei Fiori Clinic, Corso Italia , I-80011, Acerra, Naples, Italy
- Department of Advanced Biomedical Sciences, University of Naples Federico II , Via Pansini, 5, I-80131 Naples, Italy
- ORCID
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-02-20
- Volume
- 41
- Issue
- 35
- Pages
- 3346-3358
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W3007686565
- Cited by
- 191
- References
- 28
- Citations by year
- 2026: 23 · 2025: 25 · 2024: 23 · 2023: 15 · 2022: 15 · 2021: 55 · 2020: 35
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- GLP-1 receptor agonists, type 2 diabetes, major adverse cardiovascular events, cardiovascular outcomes, cardiovascular disease, myocardial infarction, stroke, cardiovascular mortality, heart failure hospitalization, drug safety, cardiovascular risk stratification, cardiovascular outcome trials, glycemic control, weight loss, blood pressure, lipid lowering, antithrombotic therapy, antihypertensive therapy
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Randomized Controlled Trials as Topic, Treatment Outcome
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