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Role of Agents for the Treatment of Diabetes in the Management of Nonalcoholic Fatty Liver Disease

  • Pharmacologic Treatment of Type 2 Diabetes (HE Lebovitz and G Bahtiyar, Section Editors)
  • Published:
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Abstract

Purpose of Review

Nonalcoholic fatty liver disease (NAFLD) is an often unrecognized complication of type 2 diabetes (T2DM) associated with significant economic burden and poor long-term hepatic and extrahepatic outcomes. Our goal is to review evidence about the complex association between NAFLD and T2DM and highlight the potential for disease co-management with the available medications used for the treatment of diabetes.

Recent Findings

A milieu of metabolic factors such as insulin resistance, glucotoxicity, and lipotoxicity, as well as genetics and other factors, contribute to the pathogenesis and co-existence of NAFLD with T2DM. The presence of T2DM in patients with NAFLD increases the risk of disease progression to steatohepatitis (NASH) and advanced fibrosis, cirrhosis, and even hepatocellular carcinoma. In addition to lifestyle modification, pioglitazone and glucagon-like peptide 1 receptor agonists (GLP-1RAs) both reduce the high cardiovascular risk and improve liver histology in patients with NAFLD. Sodium-glucose cotransporter (SGLT-2) inhibitors also appear to reverse metabolic abnormalities as well as liver disease in NAFLD, but their impact on liver histology has not been fully established. Lastly, metformin, dipeptidyl dipetidase-4 (DPP-4) inhibitors, and insulin appear to have modest to no effect on modifying the natural history of NAFLD.

Summary

Early recognition of NAFLD and monitoring for NASH with advanced liver fibrosis in patients with T2DM are crucial. The presence of NASH in a patient with T2DM should call for taking advantage of antidiabetic medications with proven efficacy to improve cardiometabolic health and prevent liver disease progression.

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Authors and Affiliations

  1. Divisions of General Internal Medicine, University of Florida, Gainesville, FL, USA

    Jeffrey Budd

  2. Division of Endocrinology, Diabetes and Metabolism, University of Florida, 1600 SW Archer Road, room H-2, Gainesville, FL, 32610, USA

    Kenneth Cusi

  3. Malcom Randall VAMC, Gainesville, FL, USA

    Kenneth Cusi

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J.B. contributed with the first draft and critical editing of the manuscript. K.C. contributed to its critical revision, editing of subsequent versions, and submission of the manuscript. Both authors reviewed and approved the final version of the manuscript.

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Correspondence to Kenneth Cusi.

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Conflict of Interest

Kenneth Cusi has received research support as principal investigator for the University of Florida from Cirius, Echosens, Inventiva, Novartis, Novo Nordisk, Poxel, and Zydus. KC is a consultant for Allergan, Astra-Zeneca, Axcella, BMS, Boehringer Ingelheim, Coherus, Eli Lilly, Genentech, Gilead, HighTide, Inventiva, Intercept, Ionis, Janssen, Pfizer, Poxel, Prosciento, Madrigal, Novo Nordisk, and Sanofi-Aventis.

Jeffrey Budd has no conflict of interest.

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Budd, J., Cusi, K. Role of Agents for the Treatment of Diabetes in the Management of Nonalcoholic Fatty Liver Disease. Curr Diab Rep 20, 59 (2020). https://doi.org/10.1007/s11892-020-01349-1

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