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Preventive effect of empagliflozin and ezetimibe on hepatic steatosis in adults and murine models

 Dong Yun Kim  ;  Kyu Sik Chung  ;  Jun Yong Park  ;  Heon Yung Gee 
 BIOMEDICINE & PHARMACOTHERAPY, Vol.161 : 114445, 2023-02 
Journal Title
Issue Date
De novo lipogenesis ; Empagliflozin ; Ezetimibe ; Non-alcoholic fatty liver disease ; Prevention
Background: Even though many oral glucose-lowering or lipid-lowering agents have already been reported to improve hepatic steatosis to some degree, which drug had a more beneficial effect on hepatic steatosis among those drugs has not been precisely explored. We analysed the effect of empagliflozi, a selective sodium-glucose cotransporter 2 inhibitor, and ezetimibe on developing hepatic steatosis.

Methods and results: Using 4005,779 patients with type 2 diabetes mellitus (T2DM) or dyslipidemia provided by the Korean National Health Insurance Service (NHIS) between January 2015 and December 2015, we analyzed the odds ratio (OR) of fatty liver development (fatty liver index [FLI] >60). Additionally, we examined the metabolic effects of ezetimibe and empagliflozin in mice fed with a choline-deficient high-fat diet, mimicking the features of human NAFLD. The experiment for agents was performed for the non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) mouse models independently. In the NHIS data, ORs for the development of fatty liver were significantly lower in all treatment groups than in the reference group, which did not receive ezetimibe or empagliflozin. (Ezetimibe therapy; OR=0.962, empagliflozin therapy; OR=0.527, ezetimibe plus empagliflozin; OR=0.509 compared to reference therapy). Unlike non-alcoholic steatohepatitis mouse model, ezetimibe, empagliflozin, and combination therapy also reduced liver steatosis in the non-alcoholic fatty liver mouse model.

Conclusions: Compared with other agents, empagliflozin and/or ezetimibe treatment reduced the risk of developing hepatic steatosis. Our data suggest that empagliflozin or ezetimibe can be primarily considered in type 2 DM or dyslipidemia patients to prevent hepatic steatosis.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Yun(김동윤)
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Jung, Kyu Sik(정규식)
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
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