Dapagliflozin in Nonalcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Mellitus Patients (T2DM).

The Hepato-protective Effect of Dapagliflozin in Type 2 Diabetes Mellitus Patients (T2DM) With Nonalcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD) encompasses conditions such as nonalcoholic steatohepatitis (NASH), which involves liver inflammation and fibrosis resulting from steatosis, potentially leading to cirrhosis and hepatocellular carcinoma. NAFLD is intricately linked to metabolic syndrome, with insulin resistance and hyperinsulinemia as key underlying factors. particularly among individuals with type2 diabetes. NAFLD is an independent risk factor for cardiovascular events, negatively impacting life expectancy in diabetic patients, and it exacerbates insulin resistance and glucose intolerance.

Early intervention in diabetes complicated by NAFLD is vital due to associations with hepatocarcinogenesis and macrovascular complications. Sodium-glucose cotransporter2 (SGLT2) inhibitors, which promote glucose excretion and reduce insulin dependence, have shown significant hypoglycemic effects, weight reduction, and potential benefits on liver function. Dapagliflozin, a specific SGLT2 inhibitor, has been proven effective in lowering hyperglycemia in type 2 diabetes and mitigating NAFLD-related complications in animal models. This study aimed to evaluate the impact of dapagliflozin on liver function in NAFLD patients with type2 diabetes. Eligible participants received dapagliflozin for 24weeks, with assessments including body composition, serum biochemistry, and molecular parameters to determine therapeutic outcomes.

Nonalcoholic fatty liver disease (NAFLD) is a general term that includes nonalcoholic steatohepatitis (NASH), which is inflammation and fibrosis that accompany steatosis and can lead to hepatic cirrhosis and hepatocellular carcinoma, as well as nonalcoholic fatty liver, which is steatosis affecting hepatocytes. including diseases including diabetes, dyslipidemia, hypertension, and poor glucose tolerance, NAFLD is closely linked to metabolic syndrome due to underlying insulin resistance and related hyperinsulinemia. Thus, NAFLD can be thought of as the metabolic syndrome's hepatic manifestation. Furthermore, between 30 and 70 percent of Egyptians have NAFLD, a consequence of type 2 diabetes. NAFLD has been demonstrated to be an independent risk factor for cardiovascular events that are directly linked to the life expectancies of diabetic patients. It also aggravates insulin resistance and plays a significant role in the decline of glucose tolerance. It is crucial to carry out early and suitable therapeutic interventions for type 2 diabetes complicated by NAFLD because disorders encompassing NAFLD/NASH are closely linked to hepatocarcinogenesis and macrovascular events, which lower life expectancy in patients with diabetes. Oral hypoglycemic medications known as sodium-glucose cotransporter 2 (SGLT2) inhibitors work in a unique way by increasing the excretion of glucose in the urine and blocking the reabsorption of glucose in the proximal renal tubule. This lowers blood sugar levels without the need for insulin. SGLT2 inhibitors not only have a great hypoglycemic impact but also lower body weight and blood glucose. Additionally, they have allegedly demonstrated positive benefits on hepatic dysfunction in both clinical trials and animal models, as well as pleiotropic effects on a variety of problems and regulatory effects on macrovascular events. Therefore, when utilized to treat patients with type 2 diabetes aggravated by NAFLD, SGLT2 inhibitors should show efficacy. It has been demonstrated that dapagliflozin, a strong and specific SGLT2 inhibitor, lowers hyperglycemia in T2DM patients. In rat models, dapagliflozin has also been shown to lessen some of the problems related to NAFLD. Thus, in this study, we assessed how dapagliflozin affected the liver function of NAFLD patients with type 2 diabetes. Dapagliflozin was given to eligible individuals for 24 weeks, and body composition tests, serum biochemistry measurements, and molecular parameters were used to assess the medication's therapeutic benefits.

Inclusion Criteria:

• Patients with Type 2 diabetes mellitus patients.
• Patients were having fatty liver changes by fibro scan and with mild to moderate elevation of serum liver enzymes or without.
• patients taking insulin or anti-diabetic medications.
• Patients have Renal dysfunction.
• Patients have Cardiac problem

Exclusion Criteria:

• Patients with a history of alcohol, smoking, uncontrolled diabetes.
• Pregnancy.
• Lactation.
• Chronic liver and decompensated liver disease in hepatitis B and C.
• patients whose abdominal ultrasounds findings were extremely abnormal (mass, fibrosis, ascites, and cirrhosis) and amino transaminase levels were severely high (ALT and AST greater than 15 times the upper limit of normal according to Johns Hopkins Diabetes Guide) suggest severe liver cell injury was also worked for acute viral hepatitis.