Cardiovascular Outcomes among New Users of GLP-1 Receptor Agonists Compared with DPP-4 Inhibitors and Sulfonylureas in Kidney Failure.

KEY POINTS: Glucagon-like peptide-1 receptor agonists are increasingly used in patients with kidney failure despite trial exclusion. Initiation was associated with a 13% lower risk of cardiovascular events and 17% lower mortality versus dipeptidyl peptidase-4 inhibitors. Initiation was associated with a 10% lower risk of heart failure hospitalization versus dipeptidyl peptidase-4 inhibitors. BACKGROUND: Few therapies improve cardiovascular outcomes for people with kidney failure. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce cardiovascular risk in patients with non-dialysis-dependent CKD, but the cardiovascular benefits in patients with kidney failure remain uncertain. The objective of this study was to compare cardiovascular outcomes among patients with kidney failure and type 2 diabetes newly initiated on GLP-1 RA versus other antiglycemic agents. METHODS: We analyzed electronic health records, Medicare claims, and Part D data from the United States Renal Data System (2011-2021) to identify new users of GLP-1 RA ( n =3629), dipeptidyl peptidase-4 inhibitors (DPP4i; n =21,369), and sulfonylureas ( n =32,296) among patients with type 2 diabetes receiving maintenance dialysis. For the primary analysis, we performed 1:1 propensity score matching of GLP-1 RA to DPP4i initiators using 61 covariates. A prespecified secondary analysis compared propensity score-matched initiators of GLP-1 RA and sulfonylureas. The primary outcome was a modified major adverse cardiovascular event (MACE) composite of myocardial infarction, stroke, or all-cause mortality. Secondary outcomes included the individual components of the primary outcome and hospitalizations for heart failure. Cause-specific Cox models were used to estimate hazard ratios (HRs). RESULTS: Among 3284 matched pairs of GLP-1 RA and DPP4i initiators, GLP-1 RA use was associated with lower risks of MACE (HR, 0.87; 95% confidence interval [CI], 0.78 to 0.97), all-cause mortality (HR, 0.83; 95% CI, 0.74 to 0.94), and heart failure hospitalization (HR, 0.90; 95% CI, 0.83 to 0.99) over up to 2 years of follow-up. Among 2792 matched pairs, GLP-1 RA and sulfonylurea initiators, GLP-1 RA was associated with lower risks of MACE (HR, 0.83; 95% CI, 0.74 to 0.93) and all-cause mortality (HR, 0.80; 95% CI, 0.69 to 0.91). CONCLUSIONS: Among patients with type 2 diabetes receiving maintenance dialysis, GLP-1 RA initiation was associated with lower risk of cardiovascular events and all-cause mortality compared with other commonly prescribed antiglycemic agents.

Duke Scholars

Author Benjamin Catanese Medicine, Nephrology

Author Daniel Edmonston Medicine, Nephrology