Cheng_2025_Front.Endocrinol.(Lausanne)_16_1647342

INTRODUCTION: The comparative kidney-protective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) in people with type 2 diabetes (T2D) with varying past estimated glomerular filtration rate (eGFR) decline rates remain unclear. METHODS: This retrospective study analyzed 4,011 propensity score-matched T2D people from a multi-center database, each with at least 2 years of eGFR data before therapy and 1 year of follow-up. The patients received either SGLT2i or DPP4i between June 2016 and December 2021. RESULTS: Among paired patients, 23.7% (SGLT2i) and 25.4% (DPP4i) were rapid decliners (<=5 mL/min/1.73 m^2/year). SGLT2i treatment was consistently associated with a slower eGFR decline than DPP4i, regardless of past eGFR slope. Post-treatment rapid eGFR decline decreased in both groups but remained higher in DPP4i users (20.5% vs. 15.4%). Those patients with past rapid eGFR decline receiving DPP4i rather than receiving SGLT2i remained at a higher risk for major adverse kidney events (MAKE) (a sustained 50% reduction in follow-up eGFR or the development of ESKD) and post-treatment rapid eGFR decline. Compared to DPP4i, SGLT2i therapy overall was associated with lower risks of MAKE (HR: 0.77; [95% CI: 0.64-0.94]), abrupt kidney function decline (HR: 0.76; [95% CI: 0.60-0.97]), and persistent rapid eGFR decline (HR: 0.76; [95% CI: 0.68-0.84]), with treatment benefits across different past eGFR decline categories. No difference in urinary albumin-to-creatinine ratio deterioration was observed between groups. The treatment benefits of SGLT2i over DPP4i were consistent across varying past eGFR slopes examined as a continuous variable. CONCLUSIONS: SGLT2i therapy was associated with better kidney outcomes and slower eGFR decline than DPP4i regardless of prior rapid eGFR decline.