Adverse kidney events with initiation of SGLT2 inhibitors versus DPP4 inhibitors in diabetic people with a history of acute kidney injury

Yi-Wei Kao; Tze-Fan Chao; Yu-Wen Cheng; Shao-Wei Chen; Yi-Hsin Chan

doi:10.1111/eci.70080

Adverse kidney events with initiation of SGLT2 inhibitors versus DPP4 inhibitors in diabetic people with a history of acute kidney injury

Eur J Clin Invest. 2025 Jun 2:e70080. doi: 10.1111/eci.70080. Online ahead of print.

Authors

Yi-Wei Kao^{1

2}, Tze-Fan Chao^{3

4}, Yu-Wen Cheng^{5

6}, Shao-Wei Chen^{7

8}, Yi-Hsin Chan^{5

6

9

10}

Affiliations

¹ Department of Applied Statistics and Information Science, Ming Chuan University, Taoyuan, Taiwan.
² Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan.
³ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁴ Institute of Clinical Medicine, Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁵ The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
⁶ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁷ Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan, Taiwan.
⁸ Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁹ School of Traditional Chinese Medicine, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
¹⁰ Microscopy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.

PMID: 40454540
DOI: 10.1111/eci.70080

Abstract

Background: The benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) in type 2 diabetes people with varying acute kidney injury (AKI) intervals or recovery remain unclear.

Methods: We retrospectively analysed 3127 paired patients with a prior history of AKI within 60 months before drug initiation, who received either SGLT2i or DPP4i between June 2016 and December 2021, utilizing 1:1 propensity score matching to balance baseline characteristics. AKI was defined as a serum creatinine (sCr) increase of ≥50% or an absolute rise of ≥.3 mg/dL. The AKI recovery was determined by comparing baseline sCr levels before drug initiation with pre-AKI values.

Results: Among patients, 17.1% on SGLT2is and 25.6% on DPP4is initiated therapy within 1 month after AKI. AKI near-full recovery (<1.1) was observed in 30.7% of SGLT2i users and 31.4% of DPP4i users before drug initiation. Compared to those with remote AKI (4-5 years prior), the risk of adverse kidney events increased only when SGLT2i therapy began within 3 months after AKI (adjusted HR: 2.15; [95% CI: 1.13-4.10]). However, for DPP4i users, the risk remained elevated for up to a year. A U-shaped association between AKI recovery and kidney outcomes was observed in DPP4i users, with both excessive (<1.0) and impaired (≥1.1) recovery increasing risk. In contrast, impaired recovery did not worsen kidney outcomes in SGLT2i users. The treatment benefits of SGLT2i over DPP4i were consistent across varying AKI intervals and recovery examined as a continuous variable.

Conclusions: SGLT2i therapy demonstrated consistent benefits across different AKI intervals and recovery levels, making it a preferable option for patients at risk of AKI.

Keywords: acute kidney injury; dipeptidyl peptidase‐4 inhibitors; sodium‐glucose cotransporter 2 inhibitors; type 2 diabetes.

Abstract

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