MACE risk lower with GLP1-RA vs DPP-4i in patients with kidney disease

The use of glucagon-like peptide-1 receptor agonists (GLP1-RAs) better protects against major adverse cardiovascular events (MACE) as compared with dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients across the spectrum of kidney disease, as shown in a retrospective study.

Researchers looked at 24,576 new users of GLP1-RA and 44,367 new users of DPP-4 inhibitors who had an estimated glomerular filtration rate (eGFR) of <90 mL/min/1.73 m². Semaglutide was the most prescribed GLP1-RA, and sitagliptin was the most prescribed DPP-4i inhibitor. The nonactive comparator cohort comprised 227,121 individuals with eGFR <90 mL/min/1.73 m² and diabetes mellitus.

Following inverse probability of treatment weighting, 24,576 GLP1-RA users and       23,600 DPP-4is were included in the analysis. The mean age was 69 years, 50 percent were female, 92 percent had type 2 diabetes mellitus, 40 percent were taking a sodium/glucose cotransporter 2 (SGLT2) inhibitor, and 41 percent had CKD stages 3-5.

The primary outcome was MACE, which comprised nonfatal myocardial infarction, unstable angina, nonfatal ischaemic stroke or transient ischemic attack, coronary revascularization, and cardiovascular death. Secondary outcomes included individual components of the composite outcome, hospitalization or emergency department visits for congestive heart failure, peripheral vascular disease revascularization, lower limb amputation, and all-cause mortality.

MACE occurred in 1,296 GLP1-RA users vs 1,374 DPP-4i users. The corresponding incidence rates were 31.6 vs 36.5 per 1,000 person-years (subdistribution hazard ratio [SHR], 0.88, 95 percent confidence interval [CI], 0.80–0.97).

The lower rate of MACE among GLP1-RA users was driven by a lower rate of cardiovascular death (SHR, 0.72, 95 percent CI, 0.62–0.85). In subgroup analyses, the association between GLP1-RA use and lower rates of MACE was not modified by CKD stages, degree of albuminuria, or concomitant use of SGLT2 inhibitors.