Glimepiride Use is Associated with Reduced Cardiovascular Mortality in Patients with Type 2 Diabetes and Chronic Heart Failure: A Prospective Cohort Study

Wu He; Gang Yuan; Yu Han; Yongcui Yan; Gen Li; Chengcheng Zhao; Jinshan Shen; Xiangrui Jiang; Chen Chen; Li Ni; Dao Wen Wang

doi:10.1093/eurjpc/zwac312

Glimepiride Use is Associated with Reduced Cardiovascular Mortality in Patients with Type 2 Diabetes and Chronic Heart Failure: A Prospective Cohort Study

Eur J Prev Cardiol. 2022 Dec 27:zwac312. doi: 10.1093/eurjpc/zwac312. Online ahead of print.

Authors

Wu He¹, Gang Yuan², Yu Han¹, Yongcui Yan¹, Gen Li¹, Chengcheng Zhao¹, Jinshan Shen³, Xiangrui Jiang³, Chen Chen¹, Li Ni¹, Dao Wen Wang¹

Affiliations

¹ Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China.
² Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

PMID: 36573717
DOI: 10.1093/eurjpc/zwac312

Abstract

Background: Glimepiride has good cardiovascular safety. However, whether glimepiride benefits clinical cardiovascular outcomes is unclear.

Methods: A total of 21,451 inpatients with type 2 diabetes (T2D) and chronic heart failure (CHF) were analyzed, including 638 who received glimepiride treatment and 20,813 who did not. Propensity score matching yielded 509 pairs (glimepiride and non-glimepiride groups), and both groups were followed up. Kaplan-Meier and Cox regression analyses were used to compare all-cause mortality, cardiovascular mortality, hospitalizations and emergency visits for heart failure, and hospitalizations for acute myocardial infarction or stroke.

Results: During follow-up, the all-cause mortality (adjusted hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.35-0.63; P < 0.001), cardiovascular mortality (adjusted HR, 0.34; 95% CI, 0.24-0.48; P < 0.001), and number of hospitalizations and emergency visits for heart failure (adjusted HR, 0.42; 95% CI, 0.36-0.50; P < 0.001) and hospitalizations for acute myocardial infarction or stroke (adjusted HR, 0.53; 95% CI, 0.38-0.73; P < 0.001) were significantly lower in the glimepiride group; the conclusion remained similar in all subgroups. Furthermore, high-dose glimepiride use (2-4 mg/day) was associated with lower cardiovascular mortality than low-dose (1 mg/day) (adjusted HR, 0.55; 95% CI, 0.31-0.99; P = 0.047). Glimepiride exhibited good molecular docking with soluble epoxide hydrolase (sEH) and increased the level epoxyeicosatrienoic acid (EET).

Conclusions: Long-term continuous glimepiride use is associated with better survival, fewer hospitalizations and emergency visits for heart failure, and fewer hospitalizations for acute myocardial infarction or stroke in patients with T2D and CHF. High-dose glimepiride has greater cardiovascular protective advantages than low-dose glimepiride. The cardiovascular protective effect of glimepiride may be related to the EET level increase through sEH inhibition.

Trial registration: ClinicalTrials.gov NCT05538819.

Keywords: Cardiovascular mortality; Chronic heart failure; Glimepiride; Mortality; Type 2 diabetes.

Plain language summary

Long-term continuous glimepiride use is associated with better survival, fewer hospitalizations and emergency visits for heart failure. High-dose glimepiride has greater cardiovascular protective advantages than low-dose glimepiride. Trial registration: ClinicalTrials.gov NCT05538819. https://www.clinicaltrials.gov/ct2/show/NCT05538819.

Associated data

ClinicalTrials.gov/NCT05538819