Effects of empagliflozin on markers of liver steatosis and fibrosis and their relationship to cardiorenal outcomes

Kahl, S., Ofstad, A. P., Zinman, B., Wanner, C., Schüler, E., Sattar, N. , Inzucchi, S. E. and Roden, M. (2022) Effects of empagliflozin on markers of liver steatosis and fibrosis and their relationship to cardiorenal outcomes. Diabetes, Obesity and Metabolism, 24(6), pp. 1061-1071. (doi: 10.1111/dom.14670) (PMID:35166009)

Abstract

Aims: Empagliflozin treatment reduced liver fat in small type 2 diabetes cohorts. This post-hoc study evaluated effects of empagliflozin on risk for non-alcoholic fatty liver disease-related steatosis and fibrosis, as well as the relationship between risk categories and cardiorenal outcomes in the randomized, placebo-controlled EMPA-REG OUTCOME trial. Materials and methods: EMPA-REG OUTCOME treated 7020 people with type 2 diabetes and cardiovascular disease with 10/25 mg/day empagliflozin or placebo. For this analysis, the Dallas steatosis index, hepatic steatosis index, non-alcoholic fatty liver disease fibrosis score and Fibrosis-4 score were calculated to assess steatosis and fibrosis risk. Changes from baseline in scores were examined by mixed model repeated measures and their associations with cardiorenal outcomes and mortality by Cox regression. Results: At baseline, 73% and 84% of participants had high steatosis risk by Dallas steatosis index and hepatic steatosis index, whereas 23% and 4% had a high risk of advanced fibrosis by non-alcoholic fatty liver disease fibrosis score and Fibrosis-4 score. Percentages of people at high steatosis risk slightly decreased with empagliflozin only, whereas empagliflozin did not improve percentages of individuals at high fibrosis risk over time compared with placebo. The high risk of advanced fibrosis at baseline related to higher risk for cardiovascular events. Effects of empagliflozin on cardiorenal and all-cause mortality outcomes were consistent across all risk groups. Conclusions: Empagliflozin may reduce steatosis but not fibrosis risk in individuals with type 2 diabetes and cardiovascular disease. The improvements in cardiorenal outcomes and mortality associated with empagliflozin therapy appear to be independent of steatosis and fibrosis risk.

• Item Type: Articles
• Additional Information: The research of the authors is supported by grants from the German Federal Ministry of Health and the Ministry of Culture and Science of the State North Rhine-Westphalia to the German Diabetes Center, the German Federal Ministry of Education and Research to German Center for Diabetes Research. MR is further supported by grants from the European Funds for Regional Development (EFRE-0400191), EUREKA Eurostars-2 (E!113230DIA-PEP) and the German Science Foundation (CRC/SFB1116/2 B12; RTG/GRK 2576 vivid, Project3) and the Schmutzler Stiftung. The study was funded by Boehringer Ingelheim.
• Keywords: Antidiabetic drug, clinical trial, liver, SGLT2 inhibitor.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed
• Authors: Kahl, S., Ofstad, A. P., Zinman, B., Wanner, C., Schüler, E., Sattar, N., Inzucchi, S. E., and Roden, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Diabetes, Obesity and Metabolism
• Publisher: Wiley
• ISSN: 1462-8902
• ISSN (Online): 1463-1326
• Published Online: 15 February 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Diabetes, Obesity and Metabolism 24(6): 1061-1071
• Publisher Policy: Reproduced under a Creative Commons License