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Pharmacological Treatment Options for Metabolic Dysfunction-associated Steatotic Liver Disease in Patients with Type 2 Diabetes Mellitus: A Systematic Review

Abstract

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.

Citing Articles

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

Konings L, Miguelanez-Matute L, Boeren A, van de Luitgaarden I, Dirksmeier F, de Knegt R Eur J Clin Invest. 2025; 55(4):e70003.

PMID: 39937036 PMC: 11891831. DOI: 10.1111/eci.70003.

References
1.
Fan H, Pan Q, Xu Y, Yang X . Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease. Arq Bras Endocrinol Metabol. 2014; 57(9):702-8. DOI: 10.1590/s0004-27302013000900005. View

2.
Belfort R, Harrison S, Brown K, Darland C, Finch J, Hardies J . A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006; 355(22):2297-307. DOI: 10.1056/NEJMoa060326. View

3.
Palmer S, Tendal B, Mustafa R, Vandvik P, Li S, Hao Q . Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2021; 372:m4573. PMC: 7804890. DOI: 10.1136/bmj.m4573. View

4.
Parker V, Robertson D, Erazo-Tapia E, Havekes B, Phielix E, de Ligt M . Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes. Nat Metab. 2023; 5(12):2086-2093. PMC: 10730390. DOI: 10.1038/s42255-023-00938-0. View

5.
Hiruma S, Shigiyama F, Kumashiro N . Empagliflozin versus sitagliptin for ameliorating intrahepatic lipid content and tissue-specific insulin sensitivity in patients with early-stage type 2 diabetes with non-alcoholic fatty liver disease: A prospective randomized study. Diabetes Obes Metab. 2023; 25(6):1576-1588. DOI: 10.1111/dom.15006. View