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01-03-2021 | Insulins | Original Research

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Authors: Haleh Chehrehgosha, Masoud Reza Sohrabi, Faramarz Ismail-Beigi, Mojtaba Malek, Mohammad Reza Babaei, Farhad Zamani, Hossein Ajdarkosh, Mahmood Khoonsari, Afshin Eshghi Fallah, Mohammad E. Khamseh

Published in: Diabetes Therapy | Issue 3/2021

Abstract

Introduction

To evaluate the efficacy of empagliflozin compared to pioglitazone in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM).

Methods

In this prospective randomized, double-blind, placebo-controlled trial, we assigned 106 patients with NAFLD and T2DM to receive empagliflozin 10 mg (n = 35), pioglitazone 30 mg (n = 34), or placebo (n = 37) for 24 weeks. Liver fat content and liver stiffness were measured using fibroscans. Body composition assessment was performed by dual-energy x-ray absorptiometry (DEXA) scans. The primary end point was change from baseline in liver steatosis, using the controlled attenuation parameter (CAP) score.

Results

A borderline significant decrease in CAP score was observed with empagliflozin compared to placebo, mean difference: − 29.6 dB/m (− 39.5 to − 19.6) versus − 16.4 dB/m (− 25.0 to − 7.8), respectively; p = 0.05. Using multivariate analysis, we observed a significant reduction in the placebo-corrected change in liver stiffness measurement (LSM) with empagliflozin compared to pioglitazone: − 0.77 kPa (− 1.45, − 0.09), p = 0.02, versus 0.01 kPa (95% CI − 0.70, 0.71, p = 0.98), p for comparison = 0.03. Changes in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), HOMA2-IR, fibrosis-4 index (FIB4 index), NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index (APRI), android/gynecoid ratio (A/G ratio), and skeletal muscle index (SMI) were comparable between the two treatment groups, while significant reductions of the body weight and visceral fat area were observed only in the empagliflozin group (p < 0.001 and p = 0.01, respectively) and both were increased in the placebo and pioglitazone groups. There were no serious adverse events in either group.

Conclusion

Treatment for 24 weeks with empagliflozin, in contrast to pioglitazone, was associated with improvement of liver steatosis and fibrosis in patients with NAFLD and T2DM. In addition, body weight and abdominal fat area were decreased in the empagliflozin group.

Trial Registration

Iranian Registry of Clinical Trials (IRCT), IRCT20190122042450N3.

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Title: Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Haleh Chehrehgosha
Masoud Reza Sohrabi
Faramarz Ismail-Beigi
Mojtaba Malek
Mohammad Reza Babaei
Farhad Zamani
Hossein Ajdarkosh
Mahmood Khoonsari
Afshin Eshghi Fallah
Mohammad E. Khamseh
Publication date: 01-03-2021
Publisher: Springer Healthcare
Keywords: Insulins
Pioglitazone
Empagliflozin
Fatty Liver
Insulins
Type 2 Diabetes
Published in: Diabetes Therapy / Issue 3/2021
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI: https://doi.org/10.1007/s13300-021-01011-3

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Other articles of this Issue 3/2021

A Pragmatic Study of Basal and Mid-Mixture Insulins as Starter Insulins in Chinese Patients With Type 2 Diabetes: Observations From Long-Term, Real-World Experience

Outcomes in GLP-1 RA-Experienced Patients Switching to Once-Weekly Semaglutide in a Real-World Setting: The Retrospective, Observational EXPERT Study

Risk Factors for Albuminuria in Normotensive Older Adults with Type 2 Diabetes Mellitus and Normal Renal Function: A Cross-Sectional Study

Effects of Increasing Metformin Dose vs Adding/Switching to Dipeptidyl Peptidase-4 Inhibitors on Glycemic Control in Patients with Type 2 Diabetes

What’s in a Name? Redefining Type 2 Diabetes Remission

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials