Clinical Trial: Semaglutide Versus Placebo in NIT-Assessed MASH-A Multicenter Randomised Placebo-Controlled Trial...

Area of Science:

• Hepatology and Gastroenterology
• Pharmacology and Drug Development
• Biomarkers and Diagnostics

Background:

• Metabolic dysfunction-associated steatohepatitis (MASH) requires effective non-invasive tests (NITs) for patient assessment.
• Semaglutide shows promise for MASH treatment, necessitating validated methods for eligibility and response monitoring.
• Current clinical practice guidance needs robust data on NIT utility in MASH management.

Purpose of the Study:

• To evaluate the utility of NITs in assessing eligibility for semaglutide treatment in patients with suspected MASH.
• To determine the effectiveness of NITs in monitoring treatment response to semaglutide compared to placebo.
• To provide randomized controlled trial (RCT) data supporting NIT-based management of MASH.

Main Methods:

• A multicenter, randomized, double-blind, placebo-controlled 52-week trial.
• Patients with MASLD and specific criteria (BMI, liver stiffness ≥8 kPa, FAST score ≥0.5) were randomized to semaglutide 2.4 mg or placebo.
• Primary outcome: change in FAST score; secondary outcomes: changes in body weight, MRI-PDFF, ALT, AST, GGT, HbA1c, and LDL cholesterol.

Main Results:

• Semaglutide significantly reduced FAST scores compared to placebo (p=0.002).
• More semaglutide recipients achieved ≥5% weight loss (64% vs. 8.3%) and ≥30% MRI-PDFF reduction (60% vs. 17%).
• Semaglutide demonstrated significant improvements in ALT, AST, GGT, HbA1c, and LDL cholesterol (p<0.05).

Conclusions:

• A NIT-based approach is feasible and effective for identifying at-risk MASH patients for semaglutide treatment.
• The FAST score, ALT, AST, and MRI-PDFF are validated NITs for monitoring semaglutide treatment response in MASH.
• This RCT provides crucial data for integrating NITs into MASH clinical practice guidance.