Nature communicationsAug 30, 2026

Heart and blood vessel outcomes of two diabetes drugs in kidney failure patients with heart failure

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 1, 2026

Abstract

In the primary ESKD-HF population, GLP-1 receptor agonists are associated with a 31.7% risk of primary composite ischemic cardiovascular events plus heart failure exacerbations, compared to 41.4% for DPP-4 inhibitors.

GLP-1 receptor agonists may reduce the risk of ischemic events (HR 0.74) and heart failure exacerbations (HR 0.76).
All-cause mortality is associated with lower risk in patients using GLP-1 receptor agonists (HR 0.68).
A death-inclusive composite outcome shows decreased risk for those on GLP-1 receptor agonists (HR 0.72).
Results are consistent across various multivariable models and prespecified subgroups.
Findings are corroborated in a confirmatory subset of patients coded for dialysis dependence (HR 0.71).

Simplified

Patients with end-stage kidney disease (ESKD) receiving maintenance dialysis have a high burden of heart failure (HF), with cardiovascular disease the leading cause of death, yet are largely excluded from randomized trials. Using the TriNetX federated electronic health record network, we emulate a target trial comparing initiation of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus dipeptidyl peptidase-4 inhibitors (DPP-4is) in diabetic ESKD patients with HF, undergoing maintenance dialysis. We identify a primary ESKD-HF population and a confirmatory dialysis-dependence-coded HF subset, and apply a new-user, active-comparator design and use propensity score matching to balance baseline characteristics. In the primary ESKD-HF population, GLP-1RAs use is associated with a lower risk of the primary composite ischemic cardiovascular events plus HF exacerbations, than DPP-4i initiation (31.7% vs. 41.4%; HR 0.72[0.64-0.82], P < 0.0001), with concordance reductions in ischemic events (HR 0.74), HF exacerbations (HR 0.76), all-cause mortality (HR 0.68), and a death-inclusive composite (HR 0.72). Results are consistent in multivariable models, across prespecified subgroups, and in extensive sensitivity analyses, and are corroborated in the confirmatory dialysis-dependence-coded HF subset HR (0.71[0.60-0.85]). These findings provide real-world evidence suggesting GLP-1RAs may improve cardiovascular outcomes in dialysis-dependent diabetic ESKD with HF and support prospective randomized evaluation.

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Heart and blood vessel outcomes of two diabetes drugs in kidney failure patients with heart failure

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