Effect of SGLT-2 inhibitors on hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus and MASLD

           Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common comorbid conditions in patients with type 2 diabetes mellitus (T2DM). Insulin resistance, dyslipidemia, and adipokine imbalance play an important role in the development of hepatic steatosis and fibrosis. In recent years, increasing evidence has shown that sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) possess not only glucose-lowering effects but also additional organ-protective properties. The study included 150 patients with type 2 diabetes mellitus. Patients were divided into four groups according to the type of glucose-lowering therapy received: patients treated with biguanides and SGLT-2 inhibitors, patients receiving SGLT-2 inhibitors combined with basal insulin therapy, patients treated with biguanides and DPP-4 inhibitors, and patients receiving biguanides with sulfonylurea therapy. Comparative assessment of hepatic steatosis, fibrosis parameters, and metabolic indicators was performed between the groups. Liver status was evaluated using FibroScan transient elastography. The degree of steatosis was assessed using the controlled attenuation parameter (CAP, dB/m), while liver fibrosis was evaluated using liver stiffness measurement (LSM, kPa). After 6 months of treatment, a significant decrease in FibroScan CAP values was observed in the groups treated with SGLT-2 inhibitors. In particular, CAP decreased from 267.4±35.1 dB/m to 238.6±27.4 dB/m in the biguanide + SGLT-2 inhibitor group and from 265.8±33.9 dB/m to 242.1±28.2 dB/m in the SGLT-2 inhibitor + basal insulin group (p<0.01). No significant changes were observed in the biguanide + DPP-4 inhibitor and biguanide + sulfonylurea groups. Liver fibrosis assessed by LSM demonstrated a tendency toward reduction in the SGLT-2 inhibitor groups; however, the differences were not statistically significant. At the same time, positive correlations were identified between CAP values and HOMA-IR, HbA1c, ALT, and AST levels. The strongest correlation was observed between CAP and HOMA-IR in the biguanide + sulfonylurea group (r=0.63; p<0.001). In the groups receiving SGLT-2 inhibitors, strong correlations were found between CAP values and triglycerides as well as adipokines (leptin and adiponectin). These findings indicate the important role of SGLT-2 inhibitors in reducing hepatic steatosis through their effects on lipid metabolism and adipokine imbalance. Furthermore, the relatively weaker correlations between CAP and BMI, HOMA-IR, and HbA1c in the SGLT-2 inhibitor groups may suggest independent hepatoprotective and anti-steatotic effects of these agents.