Comprehensive Evaluation of the Cardiovascular Protective Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Advanced Chronic Kidney Disease: A Real-World Evidence

Chih-Chung Shiao; Ching-Wen Chiu; Yu-Ming Chang; Ming-Che Liu; Phung-Anh Nguyen; Thanh-Phuc Phan; Chia-Te Liao; Chih-Wei Huang; Christianus Heru Setiawan; Hui-Hsin Cheng; Min-Huei Hsu; Jason C Hsu

doi:10.1159/000542132

Comprehensive Evaluation of the Cardiovascular Protective Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Advanced Chronic Kidney Disease: A Real-World Evidence

Am J Nephrol. 2024 Oct 21:1-11. doi: 10.1159/000542132. Online ahead of print.

Authors

Chih-Chung Shiao¹, Ching-Wen Chiu^{2

3}, Yu-Ming Chang¹, Ming-Che Liu^{4

5}, Phung-Anh Nguyen^{6

7

8

9}, Thanh-Phuc Phan¹⁰, Chia-Te Liao^{11

12

13}, Chih-Wei Huang^{14

15}, Christianus Heru Setiawan^{16

17}, Hui-Hsin Cheng⁵, Min-Huei Hsu^{9

18}, Jason C Hsu^{6

7

8

10}

Affiliations

¹ Division of Nephrology, Department of Internal Medicine, Camillian Saint Mary's Hospital Luodong, Yilan, Taiwan.
² School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan.
⁴ Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan.
⁵ Office of Human Research, Taipei Medical University, Taipei, Taiwan.
⁶ Clinical Data Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan.
⁷ Research Center of Health Care Industry Data Science, College of Management, Taipei Medical University, Taipei, Taiwan.
⁸ Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
⁹ Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan.
¹⁰ International Ph.D. Program in Biotech and Healthcare Management, College of Management, Taipei Medical University, Taipei, Taiwan.
¹¹ Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
¹² Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
¹³ TMU-Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical University, Taipei, Taiwan.
¹⁴ International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei, Taiwan.
¹⁵ Taipei Medical University Ringgold Standard Institution - Center for Simulation in Medical Education, Taipei, Taiwan.
¹⁶ Ph.D. Program, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
¹⁷ Faculty of Pharmacy, Sanata Dharma University, Yogyakarta, Indonesia.
¹⁸ Office of Data Science, Taipei Medical University, Taipei, Taiwan.

PMID: 39433037
DOI: 10.1159/000542132

Abstract

Introduction: Diabetes, kidney disease, and cardiovascular disease have complex interactions and coexistences that significantly worsen a patient's overall health. Previous research results have shown that SGLT2i hypoglycemic drugs can not only effectively control blood sugar in diabetic patients but also protect the kidneys and heart. This study further focuses on diabetic patients with kidney disease to explore the effectiveness of using SGLT2i hypoglycemic drugs in avoiding heart-related complications or death.

Methods: This is a multicenter retrospective cohort study using the Taipei Medical University Clinical Research Database (TMUCRD) as the data source. This study selected patients who suffered from both type 2 diabetes and chronic kidney disease from 1 January 2008 to 31 December 2020, as the research team. Integrated or separate 4-point major adverse cardiovascular events (4P-MACE) and mortality were the outcomes of this study. The Kaplan-Meier curves method and Cox proportional hazard regression analysis were used to explore the association between each influencing factor and the outcome.

Results: A total of 5,005 patients with type 2 diabetes and CKD were included in this study, of which 524 patients were stably treated with SGLT2i, 3,952 patients were treated with DPP4i, and 529 patients were treated with TZD. The results showed that the SGLT2i user group had a significantly lower risk of 4P-MACE compared with the SGLT2i nonuser group (hazard ratio [HR]: 0.68, 95% CI [0.49, 0.95], p = 0.024). The SGLT2i group had a significantly lower risk of cardiovascular mortality compared with the DPP4i and TZD groups (HR: 0.37, 95% CI [0.21, 0.65], p < 0.001; HR: 0.42, 95% CI [0.20, 0.90], p = 0.025).

Conclusion: This study found that for patients with both diabetes and kidney disease, SGLT2i is a better option than other oral hypoglycemic medications because it can significantly avoid the occurrence of heart-related complications. The results of this study can be used as a reference for clinical medication selection practice.

Keywords: 4-point major adverse cardiovascular events; Cardiovascular outcomes; Chronic kidney disease; SGLT2 inhibitors; Type 2 diabetes mellitus.