Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in patients with Type 2 Diabetes Mellitus

Abstract

Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common chronic liver disease, affecting at least one-third of the population worldwide. The more aggressive form is known as nonalcoholic steatohepatitis (NASH) and characterized by hepatocyte necrosis and inflammation. The presence of fibrosis is not uncommon. Fibrosis indicates a more aggressive course and patients with NASH that are at high-risk of cirrhosis and premature mortality, as well as at increased risk of hepatocellular carcinoma (HCC). Patients with type 2 diabetes mellitus (T2DM) are at the highest risk for the development of NASH, even in the setting of normal plasma aminotransferase levels. The presence of dysfunctional adipose tissue in most overweight and obese subjects, combined with insulin resistance, hyperglycemia, and atherogenic dyslipidemia, contribute to their increased cardiovascular risk. Many therapeutic agents have been tested for the treatment of NASH but few studies have focused in patients with T2DM. At the present moment, the only FDA-approved agents that in controlled studies have shown to significantly improve liver histology in patients with diabetes are pioglitazone and liraglutide. Current research efforts are centering on the mechanisms for intrahepatic triglyceride accumulation and for the development of steatohepatitis, the role of mitochondrial dysfunction in NASH, and the impact of improving glycemic control per se on the natural history of the disease. This brief review summarizes our current knowledge on the pharmacological agents available for the treatment of NASH to assist healthcare providers in the management of these challenging patients.

Keywords: Dipeptidyl peptidase 4 (DPP-4) inhibitors; Glucagon-like peptide-1 receptor agonists (GLP-1RA); Insulin resistance; Metformin; Nonalcoholic fatty liver disease (NAFLD); Nonalcoholic steatohepatitis (NASH); Pioglitazone; Sodium-glucose co-transporter 2 (SGLT2) inhibitors; Thiazolinediones; Type 2 diabetes mellitus.