Cardiovascular and renal outcomes between sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase 4 inhibitors in patients with chronic kidney disease stages 4 and 5: a population-based study

Abstract

Aims: Limited evidence exists regarding the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in cardiovascular and renal outcomes in patients with advanced chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m².

Methods: We enrolled patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m² who were prescribed SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) from 2016 to 2022 (n = 117,924). The primary cardiovascular outcomes included cardiovascular death, myocardial infarction, ischemic stroke, and heart failure-related admission. Renal outcomes encompassed an eGFR decline of >50 %, a doubling of serum creatinine levels, and progression to dialysis.

Results: The study included 6,730 participants [SGLT2i, n = 1,086; DPP4i, n = 5,644]. In both groups, the composite cardiovascular events developed at a rate of 13.2 events per 100 person-years (PYs) [hazard ratio (HR), 0.92; 95 % confidence interval (CI) 0.71-1.19]. The composite of renal events occurred at a rate of 18.5 and 16.2 events per 100 PYs in the SGLT2i and DPP4i groups, respectively [subdistribution HR 1.12; 95 % CI 0.91-1.38].

Conclusions: Compared to DPP4i, SGLT2i did not show superiority in the reduction of cardiovascular or renal events in CKD stage 4-5 patients.

Keywords: Cardiovascular outcome; Diabetic kidney disease; Dipeptidyl peptidase 4 inhibitor; Renal outcome; Sodium-glucose cotransporter 2 inhibitor.