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

European Journal of Clinical Investigation, vol. 55, pp. e70003

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.

Authors 9

  1. Sint Franciscus Gasthuis · Franciscus Vlietland

    Affiliation as printed

    Department of Internal Medicine Franciscus Gasthuis & Vlietland Rotterdam the Netherlands

  2. Sint Franciscus Gasthuis · Franciscus Vlietland

    Affiliation as printed

    Department of Internal Medicine Franciscus Gasthuis & Vlietland Rotterdam the Netherlands

  3. Julius Clinical Research BV (Netherlands)

    Affiliation as printed

    Julius Clinical Zeist the Netherlands

  4. Sint Franciscus Gasthuis · Franciscus Vlietland

    Affiliation as printed

    Department of Gastroenterology and Hepatology Franciscus Gasthuis & Vlietland Rotterdam the Netherlands

  5. Erasmus MC

    Affiliation as printed

    Department of Gastroenterology and Hepatology Erasmus MC Rotterdam the Netherlands

  6. Leiden University Medical Center

    Affiliation as printed

    Department of Gastroenterology and Hepatology LUMC Leiden the Netherlands

  7. Julius Clinical Research BV (Netherlands)

    Affiliation as printed

    Julius Clinical Zeist the Netherlands

  8. Amsterdam University Medical Centers

    Affiliation as printed

    Department of Internal Medicine Amsterdam UMC Amsterdam the Netherlands

  9. Erasmus MC · Sint Franciscus Gasthuis · Franciscus Vlietland · Julius Clinical Research BV (Netherlands)

    Affiliation as printed

    Department of Internal Medicine Franciscus Gasthuis & Vlietland Rotterdam the Netherlands

    Department of Internal Medicine and Endocrinology Erasmus MC Rotterdam the Netherlands

    Julius Clinical Zeist the Netherlands

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References 90