In a real-world study of nearly 69,000 Canadian patients with chronic kidney disease, GLP-1 receptor agonists reduced major cardiovascular events by 12% compared to DPP-4 inhibitors, primarily by lowering cardiovascular death by 28%.
28% reduction in cardiovascular deathGLP-1 agonists vs. DPP-4 inhibitors in CKD patients (SHR 0.72), consistent across all kidney disease stages including advanced CKD
What the researchers found
GLP-1 receptor agonist users had a significantly lower rate of major adverse cardiovascular events (MACE) compared to DPP-4 inhibitor users: 31.6 vs. 36.5 per 1,000 person-years (SHR 0.88, 95% CI 0.80–0.97). The cardiovascular death reduction was particularly striking: SHR 0.72 (95% CI 0.62–0.85), representing a 28% lower rate. There was no effect modification by CKD stage, albuminuria level, or concurrent SGLT2 inhibitor use — meaning the cardiovascular benefit was consistent regardless of kidney disease severity or other cardioprotective medications.
Why it matters
CKD patients were largely excluded from the landmark cardiovascular outcome trials that established GLP-1 drugs' heart benefits. This study fills a critical evidence gap by demonstrating that the cardiovascular protection extends across the full spectrum of kidney disease in real-world practice. For clinicians managing CKD patients with diabetes, this provides strong support for choosing GLP-1 drugs over DPP-4 inhibitors when cardiovascular risk reduction is a priority.
How the study worked
Population-based retrospective cohort study using administrative health data from Ontario, Canada. Included 24,576 new GLP-1 RA users and 44,367 new DPP-4 inhibitor users with eGFR measurements, of whom 41% had CKD stages 3-5. Inverse probability of treatment weighting with propensity scores minimized confounding. Multivariable Fine-Gray subdistribution hazard models, stratified by eGFR subgroup, evaluated the primary composite MACE outcome.
What this study cannot tell us
This is a retrospective observational study, so it cannot establish causation — only association. There was substantial missing albuminuria data. The comparison group (DPP-4 inhibitors) is an active comparator, not placebo, so the absolute cardiovascular benefit may differ from that estimated against no treatment. Selection bias may persist despite propensity score weighting. The study population was from Ontario, Canada, which may limit generalizability to other healthcare systems.
How to read the evidence
This is a large population-based observational study with nearly 69,000 patients, robust propensity score methods, and pre-specified subgroup analyses. While not a randomized trial, the large sample size, active comparator design, and consistent results across subgroups provide strong real-world evidence.
When this study was published
Published in 2026 in the American Journal of Kidney Diseases, this is among the most current and largest real-world studies examining GLP-1 agonist cardiovascular outcomes specifically in CKD populations.
The bigger picture
GLP-1 receptor agonists have emerged as transformative drugs not just for diabetes and obesity, but increasingly for cardiovascular and kidney protection. This study adds CKD patients — a group at enormous cardiovascular risk — to the populations that benefit from GLP-1 drugs. Combined with recent trials showing GLP-1 drugs slow kidney disease progression itself, the evidence increasingly supports GLP-1 agonists as foundational therapy for CKD patients with diabetes.
Questions still open
- Do newer GLP-1 drugs like semaglutide provide greater cardiovascular protection in CKD than older agents like liraglutide?
- Would adding a GLP-1 agonist to an SGLT2 inhibitor in CKD patients provide additive cardiovascular and kidney benefits?
- At what stage of CKD should clinicians prioritize GLP-1 agonists over other diabetes medications for cardiovascular protection?
Common questions
Are GLP-1 drugs safe and effective for people with kidney disease?
Should kidney disease patients switch from DPP-4 inhibitors to GLP-1 drugs?
Read the original research
Glucagon-like Peptide-1 Receptor Agonists and Risk of Major Adverse Cardiovascular Events in Patients With CKD.
American journal of kidney diseases : the official journal of the National Kidney Foundation, 87(2), 211-229.e1
Citation
Yau, Kevin; Ray, Joel G; Jeyakumar, Nivethika; Luo, Bin; Abdullah, Sheikh; Dixon, Stephanie N; Wing, Sara; Clemens, Kristin K; Castrillon-Ramirez, Fabio; Udell, Jacob A; Meraz-Munoz, Alejandro; Young, Ann; Harel, Ziv; Perl, Jeffrey; Leiter, Lawrence A; Garg, Amit X; Cherney, David Z I; Wald, Ron. (2026). Glucagon-like Peptide-1 Receptor Agonists and Risk of Major Adverse Cardiovascular Events in Patients With CKD.. American journal of kidney diseases : the official journal of the National Kidney Foundation, 87(2), 211-229.e1. https://doi.org/10.1053/j.ajkd.2025.09.010