S2404 Use of Oral Semaglutide in the Management of MASLD in Failures of Standard Therapy

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation in India. Effective pharmaceutical treatments remain limited. Semaglutide, a potent GLP-1 receptor agonist, promotes weight loss and improves insulin sensitivity. Previous studies have shown semaglutide's favorable effects on liver histology, imaging, enzymes, and cardiometabolic markers in MASLD. This study aimed to evaluate the efficacy and safety of oral semaglutide in patients with MASLD complicated by type 2 diabetes mellitus (T2DM). Methods: This was a prospective, observational, single arm, open label study. Thirty obese, diabetic MASLD patients with uncontrolled hyperglycemia failing standard MASLD treatment, were included in this study. Oral semaglutide was given along with standard treatment of lifestyle modification, saroglitazar/pioglitazone, lipid-lowering drugs (statins-wherever lipid parameters were elevated) and medications for other comorbidities as indicated and patients were followed up for 8 months. Results: After 8 months, mean weight loss was 13.14% and BMI reduction was 3.9 kg/m² (both P = 0.01). Body fat mass significantly declined (31.8 kg to 24.3 kg; P < 0.01), while skeletal muscle mass remained stable. Aspartate aminotransferase levels fell from 60.9 to 26.3 U/L (P < 0.01) and alanine aminotransferase from 67.9 to 30.3 U/L (P = 0.001). Glycemic control improved: FPG decreased from 143.7 to 110.5 mg/dL and HbA1c from 8.05% to 6.8% (both P < 0.01). Insulin sensitivity improved as HOMA-IR dropped from 4.34 to 1.77 (P < 0.01). Markers of liver fibrosis also improved: FIB-4 decreased from 3.23 to 1.76 (P = 0.007) and liver stiffness measurement from 21.1 to 12.2 kPa (P = 0.04). Hepatic steatosis showed a significant reduction, with CAP decreasing from 295.6 to 237.6 dB/m (P < 0.01). The most common side effects of oral semaglutide were nausea (33.3%) and vomiting (26.7%). Conclusion: The 8-month oral semaglutide treatment was effective and safe in patients with MASLD complicated by uncontrolled T2DM. Oral semaglutide treatment significantly improved impaired liver function, hypertriglyceridemia, insulin resistance, glycemic control, hepatic steatosis, and fibrosis while decreasing body weight. Although this study has numerous limitations, the results suggest a potential benefit of oral semaglutide in the treatment of liver steatosis and fibrosis, and further investigations/randomized controlled trials are warranted.