A Comparative Study of the Effect of Dapagliflozin Versus Empagliflozin ,Added to Metformin, on NAFLD in Patients With Type 2 Diabetes

Type 2 Diabetes Mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) are two chronic, interconnected metabolic disorders that affect millions of individuals worldwide. MASLD is currently the most prevalent chronic liver disease, with a global burden of 17 % to 46% of chronic liver disease cases. Patients with DM2 have a very high prevalence of MASLD, which can vary from 40% to 60%. In clinical settings, MASLD has been reported to share similar pathophysiological mechanisms (such as insulin resistance, defective hepatic lipid profile, and abnormal triglyceride metabolism) with type 2 diabetes and is strongly associated with it . It has been revealed that MASLD increases the risk of type 2 diabetes incidents by approximately twofold. Therefore, reducing the prevalence of MASLD could help mitigate the impact of type 2 diabetes to some extent. SGLT2 inhibitors are promising for MASLD and T2DM because they improve glucose control, promote weight loss, and have direct beneficial effects on the liver, such as reducing liver fat and inflammation. So, Sodium-Glucose Transport Protein 2 (SGLT-2) inhibitors would be promising therapeutic agents for treatment of MASLD/ Nonalcoholic Steatohepatitis (NASH) patients. Therefore, great interest should be provided towards SGLT-2i treatment that contributes to alleviation of MASLD by reduction of hyperglycaemia, improvement of systematic insulin resistance, elevation of caloric loss and reduction of body weight mostly due to glycosuria.

The management of (T2DM) and (MASLD) involves a multifaceted approach that targets the underlying pathophysiology of both diseases. Management strategies typically focus on controlling blood glucose levels, improving insulin sensitivity, and addressing the hepatic fat accumulation and inflammation that characterize MASLD.(12) Nevertheless, animal and human studies on incretin mimetics, glucagon-like peptide-1 receptor agonists (GLP-1 RA) approved for T2DM treatment, have provided indirect evidence that they may also ameliorate progression of MASLD/NASH, over other antidiabetic types in T2DM patients with MASLD. Therefore, newer antidiabetic agents with an additive MASLD-lowering effect would be of great interest.

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a promising oral treatment for T2D either as monotherapy or in combination with other antidiabetic agents. In addition to their anti-hyperglycemic effects and ability to reduce body weight, SGLT-2i seem to exert potent antioxidant and anti-inflammatory effects, making them promising candidates for MASLD treatment. SGLT2 inhibitors induce a series of modifications that have the potential to improve the liver condition in individuals with MASLD; they improve glycemic profile, reduce visceral adipose tissue, increase plasma adiponectin levels, and decrease uric acid levels; they also diminish oxidative stress and systemic inflammation and increase glucacon levels. Short and long-term follow-up studies should elucidate the role of these drugs in the prevention and attenuation of MASLD progression in early stages. The main aim of the present study is to compare the effects of two (SGLT-2)i , Dapa versus Empa, added to metformin) on liver steatosis and fibrosis for 6 monthsin patients with MASLD and T2D .