Clinical outcomes in people with type 2 diabetes and acute kidney disease: combined SGLT2i and GLP-1RA therapy vs. monotherapy

Jui-Yi Chen; Min-Hsiang Chuang; Hsuan-Wen Lai; Vin-Cent Wu

doi:10.1016/j.diabres.2025.112339

Clinical outcomes in people with type 2 diabetes and acute kidney disease: combined SGLT2i and GLP-1RA therapy vs. monotherapy

Diabetes Res Clin Pract. 2025 Jun 26:112339. doi: 10.1016/j.diabres.2025.112339. Online ahead of print.

Authors

Jui-Yi Chen¹, Min-Hsiang Chuang², Hsuan-Wen Lai³, Vin-Cent Wu⁴

Affiliations

¹ Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan City 710402, Taiwan; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, No. 901, Zhonghua Rd., Yongkang Dist., Tainan City 710402, Taiwan. Electronic address: kwuilus0101@gmail.com.
² Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan City 710402, Taiwan. Electronic address: 60028A@gmail.com.
³ Taipei Medical University, No. 250, Wuxing St., Xinyi Dist., Taipei City 110301, Taiwan. Electronic address: b101108006@tmu.edu.tw.
⁴ Department of Internal Medicine, Primary Aldosteronism Center of National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist., Taipei City 100225, Taiwan; NSARF (National Taiwan University Hospital Study Group of ARF) and TAIPAI, (Taiwan Primary Aldosteronism Investigators), Taipei, Taiwan. Electronic address: q91421028@ntu.edu.tw.

PMID: 40581158
DOI: 10.1016/j.diabres.2025.112339

Abstract

Aims: To evaluate the effectiveness of combined therapy of Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and Glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus monotherapy in patients with type 2 diabetes mellitus (T2DM) and acute kidney disease (AKD) METHODS: This cohort study used TriNetX from adults with T2DM and AKD, treated with either SGLT2i, GLP-1RAs, or both from 2012 to 2023. Outcomes were all-cause mortality, major adverse kidney events (MAKE), and major adverse cardiovascular events (MACE).

Results: Among 29,269 patients, 1,591 (5.4 %) received combined therapy, 6,327 in the SGLT2i group, and 5,968 in the GLP-1RAs group. The combined group had significantly lower risks of all-cause mortality compared to SGLT2i monotherapy (aHR = 0.53) and GLP-1RAs monotherapy (aHR = 0.43) after a mean follow-up of 2.4 years. The combined group showed lower risks of MAKE compared to SGLT2i monotherapy (aHR = 0.70) and GLP-1RAs monotherapy (aHR = 0.45) after a mean follow-up of 2.7 years. MACE risk was similar across groups. The combined group had a higher risk of hypoglycemia (aHR = 1.51), diabetic retinopathy (aHR = 1.59) compared to the SGLT2i monotherapy group.

Conclusions: Combined SGLT2i and GLP-1RA therapy offers better survival and kidney protection but requires careful monitoring for hypoglycemia and retinopathy.

Keywords: Combination; Glucagon-Like Peptide-1 Receptor Agonists; Mortality; Sodium-glucose cotransporter 2 inhibitors.