Effects of GLP-1 receptor agonists on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease: A systematic review and meta-analysis

Aim: To evaluate the cardiovascular outcomes of glucagon-like peptide-1 receptor agonists (GLP1-RA) in patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD).

Materials and methods: We searched PubMed, Ovid MEDLINE, CINAHL, and Web of Science databases for randomized controlled trials reporting event rates for a composite cardiovascular outcome of cardiovascular death, myocardial infarction, and stroke in patients with T2DM and CKD receiving GLP1-RA or placebo. Studies were restricted to those reporting specific event rates for patients with CKD separately from the overall population. We conducted a meta-analysis using a random-effects model. This meta-analysis was registered on PROSPERO (CRD42022320157).

Results: A total of four studies comprising 7130 patients was included in our analysis. Four different GLP1-RA were assessed in a population with CKD defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² . Treatment with GLP1-RA was not associated with a significant reduction in the composite cardiovascular end point of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (odds ratio (OR) 0.80; 95% confidence interval (CI), 0.59-1.07; p = 0.13) among patients with T2DM and CKD. Individual components of the composite cardiovascular end point were assessed in two trials and did not show evidence of an effect of GLP1-RA in reducing cardiovascular end points.

Conclusions: Pooled analysis of clinical trials reporting separate cardiovascular events rates in patients with T2DM and CKD did not find GLP1-RA to be associated with a reduction in composite cardiovascular event rates. Select GLP1-RA may offer cardiovascular event reduction in patients with T2DM and CKD, but this does not appear to be a class effect. Use of GLP1-RA with demonstrated cardiovascular benefits should be preferred in patients with CKD and T2DM to further reduce cardiovascular risk.