Effect of SGLT2 inhibitors versus DPP4 inhibitors on major adverse kidney events in diabetic people with varied kidney function decline

TL;DR

SGLT2 inhibitors are more effective than DPP4 inhibitors in slowing kidney function decline in people with type 2 diabetes, regardless of their prior kidney function decline rate.

Contribution

This study demonstrates that SGLT2 inhibitors provide better kidney protection than DPP4 inhibitors across varying levels of prior kidney function decline in diabetic patients.

Findings

SGLT2i therapy was associated with slower eGFR decline and lower risk of major adverse kidney events compared to DPP4i.

Treatment benefits of SGLT2i were consistent across different past eGFR decline categories.

No difference in urinary albumin-to-creatinine ratio deterioration was observed between the two drug groups.

Abstract

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.

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.

Among paired patients, 23.7% (SGLT2i) and 25.4% (DPP4i) were rapid decliners (≥5 mL/min/1.73 m²/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.

SGLT2i therapy was associated with better kidney outcomes and slower eGFR decline than DPP4i regardless of prior rapid eGFR decline.

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