P1551 - Use of Oral Semaglutide in the Management of MASLD in Failures of Standard Therapy

Ayush Ayush, MBBS, MD¹, Aakash Batra, MBBS², Dhruv Kant Mishra, MBBS, MD³, Syed Uzair, MBBS, MD¹, Amit Pandita, MBBS, MD¹, Yogesh Batra, MBBS, MD, DM¹
1Apollo Hospital, Delhi, Delhi, India; 2Kasturba Medical College of Manipal, Delhi, Delhi, India; 3Yatharth Superspeciality Hospital, Delhi, Delhi, India

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. AST levels fell from 60.9 to 26.3 U/L (p< 0.01) and ALT 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%)

Discussion: 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/RCTs are warranted

Disclosures:
Ayush Ayush indicated no relevant financial relationships.
Aakash Batra indicated no relevant financial relationships.
Dhruv Kant Mishra indicated no relevant financial relationships.
Syed Uzair indicated no relevant financial relationships.
Amit Pandita indicated no relevant financial relationships.
Yogesh Batra indicated no relevant financial relationships.

Ayush Ayush, MBBS, MD¹, Aakash Batra, MBBS², Dhruv Kant Mishra, MBBS, MD³, Syed Uzair, MBBS, MD¹, Amit Pandita, MBBS, MD¹, Yogesh Batra, MBBS, MD, DM¹. P1551 - Use of Oral Semaglutide in the Management of MASLD in Failures of Standard Therapy, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.