Pharmacological treatment options for metabolic dysfunction‐associated steatotic liver disease in patients with type 2 diabetes mellitus: A systematic review

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to type 2 diabetes mellitus (T2DM) through a common root in insulin resistance. The more severe stage, metabolic dysfunction-associated steatohepatitis (MASH), increases the risk for cardiovascular complications, liver cirrhosis and hepatocellular carcinoma. Several trials investigating established antidiabetic-drugs in patients with T2DM and MASLD have yielded promising results. Therefore, we aimed to systematically review the effect of T2DM-drug treatment on MALSD parameters. METHODS: Medical databases were searched until January 2025 for controlled trials in patients with T2DM and MASLD/MASH. Studies that evaluated the effect of T2DM-medication on the severity of MASLD/MASH in T2DM patients were included. The quality of the studies was assessed by three independent reviewers using a set of Cochrane risk-of-bias tools. RESULTS: Of 1748 references, 117 studies fulfilled the inclusion-criteria and were assessed for eligibility in full-text. Fifty-two articles were included. Data included a total of 64.708 patients and study populations ranged from 9 to 50.742. Heterogeneity in study-design and analysis hampered the comparability of the results. Most evidence was present for GLP-1 receptor agonists, SGLT2-inhibitors and PPAR-γ-agonists for regression of liver fibrosis and MASH. CONCLUSION: Studies on the value of T2DM-drug treatment in the improvement of MASLD vary significantly in study design, size and quality. GLP-1 receptor agonists, PPAR-γ-agonists, SGLT2-inhibitors may all be preferred pharmacological interventions for patients with MASLD/MASH and T2DM. Newer agents like dual GLP-1/GIP or triple GLP-1/GIP/Glucagon agonists will likely play an important role in the treatment of MASLD/MASH in the near future.