Role of Agents for the Treatment of Diabetes in the Management of Nonalcoholic Fatty Liver Disease
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PHARMACOLOGIC TREATMENT OF TYPE 2 DIABETES (HE LEBOVITZ AND G BAHTIYAR, SECTION EDITORS)
Role of Agents for the Treatment of Diabetes in the Management of Nonalcoholic Fatty Liver Disease Jeffrey Budd 1 & Kenneth Cusi 2,3 Accepted: 10 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Liver fat . Steatosis . NAFLD . Insulin resistance . Nonalcoholic steatohepatitis . NASH . Cirrhosis . Type 2 diabetes . Pioglitazone . Glucagon-like peptide 1 receptor agonist . Sodium-glucose cotransporter 2 inhibitors . Dipeptidyl dipetidaase-4 (DPP-4) inhibitors . Insulin . Sulfonylureas
Introduction Given the increased risk of morbidity and mortality associated with nonalcoholic fatty liver disease (NAFLD) [1], it is now This article is part of the Topical Collection on Pharmacologic Treatment of Type 2 Diabetes * Kenneth Cusi [email protected] 1
Divisions of General Internal Medicine, University of Florida, Gainesville, FL, USA
2
Division of Endocrinology, Diabetes and Metabolism, University of Florida, 1600 SW Archer Road, room H-2, Gainesville, FL 32610, USA
3
Malcom Randall VAMC, Gainesville, FL, USA
recognized that its early diagnosis is critical to the optimal management of patients with type 2 diabetes (T2DM) [2••, 3•, 4, 5]. As the number of people with obesity has tripled worldwide in t
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