Dapagliflozin Reduces Liver Fat Independent of Weight Loss in T2D Obesity | Feb 2026 | DOI: 10.1002/oby.70134

Introduction

In type 2 diabetes, hepatic steatosis is common and contributes to cardiometabolic risk. SGLT2 inhibitors improve weight and glycemia, but whether they reduce liver fat through weight loss alone or via a direct hepatic effect has remained uncertain.

Summary

This secondary analysis of a randomised, placebo-controlled trial studied 56 patients with type 2 diabetes assigned to placebo or dapagliflozin 10 mg for 12 months. Most participants (76%) had hepatic steatosis at baseline, and groups were comparable in metabolic risk and liver fat. Compared with placebo, dapagliflozin significantly reduced liver fat measured by MRI–proton density fat fraction (PDFF), alongside modest reductions in body weight and HbA1c. Crucially, mediation analysis showed that the reduction in liver fat was driven by a direct effect of dapagliflozin, while the indirect pathway via weight loss was not statistically significant. The findings suggest dapagliflozin can lower hepatic fat in T2D beyond its effects on weight and glycemic control, supporting further investigation of SGLT2 inhibitors as potential tools for managing metabolic dysfunction–associated steatotic liver disease.