P3740 - Semaglutide’s Dose Dependent Effect on MASH Resolution: Updated Meta-Analysis of 5 RCTs With Histologic and Metabolic Improvements

Madhu Babu Adusumilli, MD¹, Priyanka Pradhan, MD², Sweta Sahu, MBBS³, Swetha Chinthala, ⁴, Rithik Naik Korra, MBBS⁵, Tanmayee Mareedu, MBBS⁶, Namra Gohil, MBBS⁷, Heom Mahendra Bhatt, MBBS⁸, Ashwin Rumalla, MD¹
1University of Central Florida, HCA Healthcare GME, Ocala, FL; 2University of Louisville, Louisville, KY; 3J.J.M. Medical College, Bhubaneswar, Orissa, India; 4Davao Medical School Foundation Inc, Davao, Davao del Sur, Philippines; 5Osmania General Hospital and Medical College, Hyderabad, Telangana, India; 6Mamata Academy of Medical Sciences, Hyderabad, Telangana, India; 7Medical College Baroda, Vadodara, Gujarat, Vadodara, Gujarat, India; 8Dr.M.K.Shah medical College and Research centre, Bagasara, Gujarat, India

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is a rapidly growing global health concern. Semaglutide, a GLP-1 receptor agonist, treats MASH comorbidities like obesity and type 2 diabetes. Given MASH's increasing burden and evidence of semaglutide efficacy, this meta-analysis assessed the drug’s utility using a larger patient population from recent trials and compared efficacy at different dosages.

Methods: A random effects meta-analysis (Der Simonian-Laird method) was performed using R (v4.3.1) on 5 RCT’s (n=1,366) which evaluated semaglutide’s efficacy in adults with biopsy-proven MASH. The primary outcomes included MASH resolution without worsening fibrosis and stage-1 fibrosis improvement without worsening MASH. The secondary outcomes included changes in MRI-proton density fat fraction (MRI-PDFF), body weight, and liver enzymes (ALT/AST). Another objective was to compare the efficacy across different dosing regimens of semaglutide.

Results: Our meta-analysis analyzed 3 RCTs (n=1,191) from 5 RCTs for the primary endpoint, as two studies lacked biopsy confirmed follow-up data. The primary outcome of MASH resolution had an odds ratio (OR) of 4.56 (95% CI: 1.78-11.67). We observed only a trend towards fibrosis improvement (OR 1.56, 95% CI: 0.55–4.41), which was not significant. MASH resolution rates increased with higher doses, from 32.8% in the ESSENCE trial (2.4 mg/week for ≥72 weeks) to 59% in the Newsome trial (0.4 mg/day for 72 weeks), with fibrosis improvement of 37% and 43%, respectively. For secondary outcomes, 5 RCTs showed significant results favoring semaglutide with 50% reduction in MRI-PDFF, 10–13% decrease in body weight, and up to 40%/30% reductions in ALT/AST.

Discussion: This meta-analysis showed that semaglutide was statistically better at resolving MASH versus placebo. There was a 26.2% increase in MASH resolution rates at higher doses of semaglutide (0.4 mg daily/2.8 mg weekly) compared to 2.4 mg weekly. The results for fibrosis improvement were not significant, but reductions in MRI-PDFF, body weight, and hepatic enzyme levels were observed. Given good compliance and no increased side effects with higher semaglutide dosage, it appears optimal for long-term use. Future studies are needed on dose-dependent outcomes and therapy duration of semaglutide and other GLP-1 receptor agonists.

Disclosures:
Madhu Babu Adusumilli indicated no relevant financial relationships.
Priyanka Pradhan indicated no relevant financial relationships.
Sweta Sahu indicated no relevant financial relationships.
Swetha Chinthala indicated no relevant financial relationships.
Rithik Naik Korra indicated no relevant financial relationships.
Tanmayee Mareedu indicated no relevant financial relationships.
Namra Gohil indicated no relevant financial relationships.
Heom Mahendra Bhatt indicated no relevant financial relationships.
Ashwin Rumalla indicated no relevant financial relationships.

Madhu Babu Adusumilli, MD¹, Priyanka Pradhan, MD², Sweta Sahu, MBBS³, Swetha Chinthala, ⁴, Rithik Naik Korra, MBBS⁵, Tanmayee Mareedu, MBBS⁶, Namra Gohil, MBBS⁷, Heom Mahendra Bhatt, MBBS⁸, Ashwin Rumalla, MD¹. P3740 - Semaglutide’s Dose Dependent Effect on MASH Resolution: Updated Meta-Analysis of 5 RCTs With Histologic and Metabolic Improvements, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.