Sodium-Glucose Cotransporter 2 Inhibitors Reduce the Risk of Hospitalization for Heart Failure and Amputation Rate Compared With Incretin-Based Therapy in Patients With Diabetic Foot Disease: A Nationwide Population-Based Study

Yi-Hsuan Lin; Chia-Hung Lin; Yu-Chih Lin; Yu-Yao Huang; An-Shun Tai; Shih-Chen Fu; Sheng-Hsuan Lin

doi:10.1016/j.eprac.2024.01.016

Sodium-Glucose Cotransporter 2 Inhibitors Reduce the Risk of Hospitalization for Heart Failure and Amputation Rate Compared With Incretin-Based Therapy in Patients With Diabetic Foot Disease: A Nationwide Population-Based Study

Endocr Pract. 2024 Feb 5:S1530-891X(24)00062-4. doi: 10.1016/j.eprac.2024.01.016. Online ahead of print.

Authors

Yi-Hsuan Lin¹, Chia-Hung Lin², Yu-Chih Lin³, Yu-Yao Huang⁴, An-Shun Tai⁵, Shih-Chen Fu⁵, Sheng-Hsuan Lin⁶

Affiliations

¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan.
² Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan; Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
⁴ Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Medical Nutrition Therapy, Chang Gung Memorial Hospital, Linkou, Taiwan.
⁵ Institute of Statistics, National Chiao Tung University, Hsinchu, Taiwan.
⁶ Institute of Statistics, National Chiao Tung University, Hsinchu, Taiwan. Electronic address: shenglin@stat.nctu.edu.tw.

PMID: 38325629
DOI: 10.1016/j.eprac.2024.01.016

Abstract

Objective: Major adverse cardiovascular event (MACE) outcomes associated with sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapies remain unclear in patients with type 2 diabetes and newly diagnosed diabetic foot complications (DFCs). This study examined the impact of SGLT2i and GLP-1 RA use on the rates of MACEs and amputations in patients with type 2 diabetes and without cardiovascular disease.

Methods: Data from the Taiwan National Health Insurance Research Database (2004-2017) were analyzed, focusing on patients with type 2 diabetes without previous MACE and newly diagnosed DFCs. The primary outcome was the first MACE occurrence, and the secondary outcomes included MACE components, all-cause mortality, and lower extremity amputation (LEA) rates.

Results: SGLT2i users showed a significant decrease in the MACE (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.46-0.88) and hospitalization for heart failure (HR, 0.54; 95% CI, 0.35-0.83) rates compared with dipeptidyl peptidase-4 inhibitor users. The amputation rates were also lower in SGLT2i users without LEA at the first DFC diagnosis (HR, 0.28; 95% CI, 0.10-0.75) and did not increase in those with a history of peripheral artery disease or LEA. No significant differences were observed between dipeptidyl peptidase-4 inhibitor and GLP-1 RA users in terms of the primary or secondary outcomes.

Conclusion: In patients with type 2 diabetes initially diagnosed with DFC, SGLT2i are effective in significantly reducing the hospitalization for heart failure and MACE rates. SGLT2i lower the amputation rates, especially in patients who have not previously had a LEA, than the dipeptidyl peptidase-4 inhibitor therapy.

Keywords: GLP-1 receptor agonist; SGLT2 inhibitors; amputation rate; diabetic foot complications; major adverse cardiovascular events; type 2 diabetes mellitus.