Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Several lines of evidence have indicated a pathogenic role of insulin resistance, and a strong association with type 2 diabetes (T2MD) and metabolic syndrome. Importantly, NAFLD appears to enhance the risk for T2MD, as well as worsen glycemic control and cardiovascular disease in diabetic patients. In turn, T2MD may promote NAFLD progression. The opportunity to take into account NAFLD in T2MD prevention and care has stimulated several clinical studies in which antidiabetic drugs, such as metformin, thiazolidinediones, GLP-1 analogues and DPP-4 inhibitors have been evaluated in NAFLD patients. In this review, we provide an overview of preclinical and clinical evidences on the possible efficacy of antidiabetic drugs in NAFLD treatment. Overall, available data suggest that metformin has beneficial effects on body weight reduction and metabolic parameters, with uncertain effects on liver histology, while pioglitazone may improve liver histology. Few data, mostly preclinical, are available on DPP4 inhibitors and GLP-1 analogues. The heterogeneity of these studies and the small number of patients do not allow for firm conclusions about treatment guidelines, and further randomized, controlled studies are needed.
Highlights
Hepatic steatosis represents the first step of non-alcoholic fatty liver disease (NAFLD)
glucagon-like peptide-1 (GLP-1) receptors are present in human hepatocytes and their activation produces a direct effect on hepatic steatosis, increasing hepatic insulin signaling and sensitivity [156]
NAFLD is associated with a worse glycemic control and increased cardiovascular disease (CVD)/chronic kidney disease (CKD) risk in patients with established type 2 diabetes mellitus (T2DM)
Summary
Hepatic steatosis represents the first step of non-alcoholic fatty liver disease (NAFLD). The spectrum of this disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD is considered the most common cause of chronic liver disease worldwide [1,2]. In the general US population, the prevalence of NAFLD is estimated to be approximately 30% [3], but much higher estimates are reported in selected high-risk populations, such as Hispanics, obese persons, and patients with type 2 diabetes mellitus (T2DM) or with metabolic syndrome [2]. NAFLD is, a complex disease with clinical and therapeutic implications beyond the liver disease. In the light of the strong link between NAFLD and T2DM, our review discusses the possible role of antidiabetic drugs in NAFLD therapy, and underlines the need to take into account NAFLD in diabetes prevention and care
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