ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Clinical Diabetes
This article is part of the Research TopicPharmaceutical Care and Wellness of DiabetesView all 11 articles
Effect of SGLT2 inhibitors versus DPP4 inhibitors on major adverse kidney events in diabetic people with varied kidney function decline
Provisionally accepted
- 1Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
- 2Ming Chuan University - Taoyuan Campus, Taoyuan, Taiwan
- 3Taipei Veterans General Hospital, Taipei City, Taiwan
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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 4011 propensity score-matched T2D people from a multi-center database, each with at least two-years of eGFR data before therapy and one year of follow-up. 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 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 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.
Keywords: Sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 inhibitors, type 2 diabetes, Estimated glomerular filtration rate, Acute Kidney Injury
Received: 15 Jun 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Cheng, Kao, Chen, 詹 and Chao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
益欣 詹
Tze-Fan Chao
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