The Emerging Role of Anti-Hyperglycemic Agents for the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease

The prevalence of type 2 diabetes mellitus (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing worldwide. MASLD, previously known as non-alcoholic fatty liver disease (NAFLD), is defined as a condition of steatotic liver disease (SLD) with one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The variety of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). Subjects with T2D have a doubled risk of developing MASLD, and vice versa. Furthermore, the presence of T2D is considered a risk factor for cirrhosis, hepatocellular carcinoma and liver-related mortality in patients with MASLD as well as the presence of MASLD is associated with adverse outcomes in T2D population, including cardiovascular and chronic kidney diseases. The relationship between MASLD and T2D is bidirectional. Given the fact that a mutually detrimental relationship between T2D and MASLD exists, the approach to managing MASLD is undergoing a trasformative phase, with increasing attention toward the use of anti-hyperglycemic agents. In this review, we explore the emerging role of anti-hyperglycemic agents in the context of MASLD treatment, examining the latest scientific evidence and assessing the effectiveness of these novel approaches. Understanding the interconnection between diabetes and MASLD could open new therapeutic perspectives and guide the formulation of more effective treatment protocols for this growing metabolic epidemic.