Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent liver disease in the world, yet there are still no approved pharmacological therapies to prevent or treat this condition. NAFLD encompasses a spectrum of severity, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Although NASH is linked to an increased risk of hepatocellular carcinoma and cirrhosis and has now become the leading cause of liver failure-related transplantation, the majority of patients with NASH will ultimately die as a result of complications of type 2 diabetes mellitus (T2DM) and cardiometabolic diseases. Importantly, NAFLD is closely linked to obesity and tightly interrelated with insulin resistance and T2DM. Thus, targeting these interconnected conditions and taking a holistic attitude to the treatment of metabolic disease could prove to be a very beneficial approach. This Review will explore the latest relevant literature and discuss the ongoing therapeutic options for NAFLD focused on targeting intermediary metabolism, insulin resistance and T2DM to remedy the global health burden of these diseases. Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are closely linked; effective therapeutics are lacking for both conditions, particularly NAFLD. This Review will discuss therapeutic options for NAFLD, focusing on targeting intermediary metabolism, insulin resistance and T2DM. Key points Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease globally, yet there are currently no approved therapies. While NAFLD progression to non-alcoholic steatohepatitis is becoming the leading cause of end-stage liver failure, the leading causes of death in patients with NAFLD are complications of cardiometabolic disease. A tight relationship exists between NAFLD, insulin resistance and type 2 diabetes mellitus. It is likely that developing therapeutics that target both NAFLD and cardiometabolic risk factors might be extremely beneficial.