Effect of oral Semaglutide vs Dapagliflozin on hepatic steatosis in patients with Type 2 Diabetes mellitus and Metabolic dysfunction-associated steatotic liver disease – a pilot study

Metabolic dysfunction-associated steatotic liver disease (MASLD) and Metabolic dysfunction-associated steatohepatitis (MASH) have recently replaced the terms Non-alcoholic fatty liver disease (NAFLD) and Non-alcoholic steatohepatitis (NASH) (1). Studies suggest a nearly complete overlap (99%) between the MASLD-defined population and the historical NAFLD-defined population (2, 3). All recommendations in the American Association for the Study of Liver Diseases (AASLD) Practice Guidance on the clinical assessment and management of NAFLD can be applied to patients with MASLD (1). So, both the terms MASLD and MASH have been interchangeably used with NAFLD and NASH, respectively, in our study paper. MASLD is the most common chronic liver disease, affecting 17-47% of the population worldwide (4). MASLD/MASH has now become one of the most common indications for liver transplantation worldwide. Type 2 diabetes mellitus (T2D) is a major risk factor for MASLD and MASH since the prevalence of MASLD is as high as 30-75% among these patients (5-7). Patients with MASH have an increased risk of morbidity and mortality related to liver and cardiovascular disease compared with patients who have simple steatosis and the general population (8-10). Early detection of severe steatosis and significant fibrosis by noninvasive methods would be useful to allow early treatment of MASLD in high-risk patients with T2D. The strong association of MASH with metabolic syndrome provides a compelling rationale for the investigation of Glucagon-like peptide-1 receptor agonists (GLP1RA) that induce weight loss and insulin sensitivity. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are oral antidiabetic drugs that reduce hyperglycemia independently of insulin secretion by promoting glucosuria and weight loss (11). In animal studies, SGLT2i have been found to suppress the development of NAFLD /NASH (12).  Few human trials have investigated the effect of SGLT-2i on hepatic steatosis in patients with T2D and NAFLD (13, 14). In March 2024, a drug named Resmetirom was approved by the Food and Drugs Administration (FDA) for the treatment of patients with non-cirrhotic MASH and moderate to advanced hepatic fibrosis (15).  However, there has been a significant unmet medical need for effective and accessible treatment for MASLD.  Our study is an attempt to explore two drugs thatare routinely used in the treatment of T2D for the treatment of MASLD.