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

BACKGROUND/AIMS: Non-invasive test (NIT)-based assessment of eligibility and treatment response with semaglutide is needed to inform clinical practice guidance. Therefore, utilising a randomised, placebo-controlled study design, we evaluated the utility of NITs to assess eligibility and treatment response in patients with suspected at-risk MASH randomised to semaglutide versus placebo. METHODS: In this multicentre, randomised, double-blind placebo-controlled 52-week trial, patients meeting AASLD criteria for MASLD with BMI ≥ 27 kg/m, or BMI ≥ 25 kg/m and prediabetes or type 2 diabetes with liver stiffness by VCTE ≥ 8 kPa and a FAST score ≥ 0.5 were randomised to either semaglutide 2.4 mg subcutaneously weekly or placebo. The primary outcome was change in the FAST score at end of treatment from baseline. Other endpoints included changes in body weight, MRI-PDFF, ALT and HbA1c. RESULTS: Fifty-five participants were randomised (55% women, 20% with diabetes). Mean (SD) age, BMI, and FAST at baseline were 48.8 (14) years, 40.2 (15) kg/m, 0.62 (0.12), respectively. The semaglutide group had a significantly greater reduction in FAST compared with placebo (-0.28 vs. -0.12; p = 0.002). More semaglutide recipients achieved ≥ 5% weight loss (64% vs. 8.3%; p < 0.001) and ≥ 30% reduction in MRI-PDFF (60% vs. 17%; p = 0.047). Semaglutide led to a significantly greater reduction in ALT, AST, GGT, HbA1c and LDL cholesterol (p < 0.05). Gastrointestinal-related adverse events were common but not significantly different between the two groups (p = 0.59). CONCLUSIONS: A NIT-based approach to identify at-risk MASH patients for semaglutide treatment is feasible and effective. This study provides RCT data showing that FAST, ALT, AST and MRI-PDFF can be used to monitor treatment response.