Kidney outcomes associated with sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide 1 receptor agonists: A real-world population-based analysis

Abstract

Background Kidney benefits have been demonstrated for both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) compared with placebo in patients with type 2 diabetes. This study aimed to compare the impacts of SGLT2i and GLP1RA on the trend of estimated glomerular filtration rate (eGFR) and other kidney outcomes. Methods Using a real-world population-based database, the Hong Kong Hospital Authority (HA) database, of patients with type 2 diabetes between January 2008 and December 2020, patients started on SGLT2i were compared with those started on GLP1RA, with one-to-one propensity-score matching. Primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), incident macroalbuminuria and kidney-related mortality. Secondary outcome was the rate of eGFR decline. Findings A total of 2551 SGLT2i and 2551 GLP1RA new users were analyzed. At baseline, mean age was 56·2 years, with mean eGFR 78·0 mL/min/1·73m2 and 11·9% having macroalbuminuria. Upon median follow-up of 13 months (IQR: 5-27), SGLT2i users had a lower risk of composite kidney outcomes (HR=0·77, 95%CI 0·62–0·96, p = 0·02), mainly driven by a reduction in ESKD (HR=0·53, p = 0·01). SGLT2i users also tended to have a lower risk of incident macroalbuminuria (HR=0·74, p = 0·05). Subgroup analyses of the benefits of SGLT2i use on composite kidney outcomes did not reveal interaction by age, sex, baseline eGFR/albuminuria status, hemoglobin A1c (HbA1c) and renin-angiotensin-system inhibitor use. Furthermore, SGLT2i users had a slower eGFR decline than GLP1RA users (SGLT2i: -1·19 mL/min/1·73m2/year, GLP1RA: -1·95 mL/min/1·73m2/year, p < 0·01). Interpretation Our results suggest that SGLT2i might be superior to GLP1RA in reducing kidney outcomes among patients with type 2 diabetes. Future trials are needed to corroborate our findings. Funding None.