Metabolic dysfunction-associated steatotic liver disease and type 2 diabetes: Pathophysiology, diagnosis, and emerging therapeutic strategies

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), the updated terminology for fatty liver disease linked to metabolic dysfunction, is highly prevalent among individuals with type 2 diabetes mellitus (T2DM). MASLD affects a majority of patients with T2DM and markedly increases the risk of fibrosis, cirrhosis, hepatocellular carcinoma, and cardiovascular mortality. The pathogenesis in diabetic populations reflects a convergence of insulin resistance, dyslipidemia, mitochondrial dysfunction, chronic inflammation, and genetic predisposition. Advances in non-invasive diagnostics, including elastography and serum biomarkers, enable earlier identification and staging of disease, though limitations remain in diabetic cohorts. Lifestyle modification is the cornerstone of therapy, yet emerging pharmacotherapies are reshaping the therapeutic landscape. Antidiabetic agents such as glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and pioglitazone show hepatic benefits beyond glycemic control, while novel agents and combination regimens are under active evaluation. This narrative review synthesizes current evidence on epidemiology, mechanisms, diagnostics, and therapeutics of MASLD in T2DM, and highlights future directions in precision medicine. Integration of multidisciplinary care is essential to address this converging epidemic.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Type 2 diabetes mellitus; Insulin resistance; Hepatic fibrosis; Non-invasive diagnostics; Glucagon-like peptide-1 receptor agonists; Sodium-glucose cotransporter-2 inhibitors; Personalized medicine; Fatty liver; Metabolic associated steatohepatitis

Core Tip: Metabolic dysfunction-associated steatotic liver disease is highly prevalent among patients with type 2 diabetes mellitus, amplifying risks of fibrosis, cirrhosis, hepatocellular carcinoma, and cardiovascular disease. The pathogenesis reflects overlapping mechanisms of insulin resistance, dyslipidemia, inflammation, and genetic predisposition. This narrative review integrates updated evidence on epidemiology, diagnostics, and therapeutics, emphasizing the roles of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and emerging agents. A multidisciplinary, personalized approach remains essential to reduce the burden of this increasingly recognized disease spectrum.