Antidiabetic Agents in the Management of Hepatic Fibrosis in Type 2 Diabetes Mellitus and MASLD/MASH: A Narrative Review

Abstract

Hepatic fibrosis is a pathological process resulting from chronic liver injury that represents the primary determinant of disease progression toward cirrhosis and cardiovascular complications. In patients with type 2 diabetes mellitus (T2DM), the risk of hepatic fibrosis is significantly elevated, particularly in the context of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). This article aims to review antidiabetic agents with evidence supporting hepatic fibrosis reduction, as well as those lacking such evidence. Different classes of antidiabetic drugs demonstrate divergent effects on hepatic steatosis, steatohepatitis, and fibrosis. Pioglitazone exhibits the most consistent evidence for improving the histological features of MASH and reducing fibrosis stage with long-term therapy. GLP-1 receptor agonists and dual GIP/GLP-1 agonists demonstrate significant effects on body weight reduction and steatohepatitis improvement, with growing evidence of fibrosis benefit. SGLT2 inhibitors confer benefits through improvement of steatosis and non-invasive fibrosis markers, alongside robust cardiovascular and renoprotective effects. In contrast, metformin, DPP-4 inhibitors, insulin, and sulfonylureas do not demonstrate meaningful evidence of hepatic fibrosis reduction. Weight loss of 7–10% remains the most consistently identified factor correlated with fibrosis regression. Therapeutic selection must therefore be individualized, comprehensive, and guided by the patient’s comorbidity profile.