Diabetes and NAFLD: a high-risk cohort with definite therapeutic potential

Despite the fact that non-alcoholic fatty liver disease (NAFLD) and its severe clinical forms [non-alcoholic steatohepatitis (NASH) and NASH-cirrhosis] are highly prevalent in the general population, there are no licensed drugs for NAFLD, and lifestyle intervention remains the only treatment accepted by international guidelines. This is despite massive investments in research by pharmaceutical companies. In the presence of type 2 diabetes, novel anti-diabetic drugs offer an opportunity to reduce the burden of NAFLD, by adequate control of glucose and lipid metabolism, also reducing the risk of NASH progression, advanced fibrosis, and finally hepatocellular carcinoma. We extensively reviewed the literature, based either on registration studies, ad hoc randomized studies or real-world data, to define the effectiveness of anti-diabetic drugs in the treatment of NAFLD and prevention of hepatocellular carcinoma (HCC). Metformin provides the best evidence for decreased risk of HCC, pioglitazone was associated with decreased progression to fibrosis, glucagon-like peptide-1 receptor agonists offer a possible opportunity to reduce NAFLD progression coupled with a definite protection for cardiovascular outcomes, and sodium-glucose cotransporter-2 inhibitors are likely to reduce lipid burden, simultaneously reducing the risk of progressive renal and heart failure. For the latter two drug classes, the effects on NAFLD might largely explained by decreased body weight, in keeping with the beneficial effects of intensive lifestyle intervention.