Cardiovascular outcome of Glucagon-Like Peptide-1 Receptor Agonists vs Dipeptidyl Peptidase-4 Inhibitor on End-stage Renal Disease patients with Heart Failure: An Emulated Target Trial in Patients with Diabetes

Abstract Globally, an estimated 4.6 million individuals live with end-stage renal disease (ESRD), with cardiovascular disease the leading cause of death. Heart failure (HF) affects over one-third of dialysis patients, yet effective therapies remain scarce as trials largely excluded this population. Using TriNetX, we emulated a target trial comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) with dipeptidyl peptidase-4 inhibitors (DPP-4is) in ESRD patients with HF. Among 5,087 eligible patients, 1:1 propensity score matching yielded 1,257 pairs. GLP-1RAs use was associated with risk reduction of the primary composite of ischemic cardiovascular events and HF exacerbations (30.1% vs. 40.1%; HR 0.71(0.62–0.81), p<0.001), lowering ischemic events (HR 0.69), HF exacerbations (HR 0.73), and mortality (HR 0.67). Subgroup analyses showed benefit across prevention settings, baseline therapy, and HF subtypes. Findings suggest GLP-1RAs may provide cardiovascular benefit in ESRD patients with HF, a high-risk group underserved in clinical trials, and warrant confirmation in randomized studies.