Semaglutide outcomes in Japanese patients with MASH align with results from the overall ESSENCE trial population

By
Hayato Nakagawa
October 27, 2026

Journal Of Gastroenterology

Overview

In a Japanese subgroup of the phase 3 ESSENCE trial, semaglutide 2.4 mg weekly was associated with MASH resolution without worsening fibrosis in 63.1% of participants, compared with 36.8% receiving placebo, closely matching the overall trial results. Fibrosis improvement and safety findings were broadly consistent with the global population, although the subgroup was small and the fibrosis treatment difference was imprecise.

Background

MASH is a progressive form of MASLD associated with fibrosis and increased risk of liver-related outcomes. The source reports that semaglutide was approved in Japan in June 2026 for non-cirrhotic MASH with F2–F3 fibrosis, based on the global ESSENCE trial. Japanese patients may have lower BMI than Western populations, making it important to assess whether trial findings apply across differences in body size. A Japanese nationwide cohort cited in the source found similar risks of liver-related events among lean and non-lean people with MASLD.

Data Highlights

Outcome	Japanese semaglutide	Japanese placebo	Overall ESSENCE semaglutide	Overall ESSENCE placebo
MASH resolution without worsening fibrosis	63.1%	36.8%	62.9%	34.3%
Fibrosis improvement without worsening steatohepatitis	36.5%	28.9%	36.8%	22.4%
Mean percentage weight loss	11.4%	Not reported in source	10.5%	Not reported in source
Participants in Japanese subgroup	78	38	116 Japanese participants among first 800 randomized
Mean baseline BMI	29.8 kg/m²	Not reported by treatment arm	34.3 kg/m² overall population

Key Findings

Among 116 Japanese participants in the first 800 randomized ESSENCE participants, 78 received semaglutide 2.4 mg weekly and 38 received placebo.
MASH resolution without worsening fibrosis occurred in 63.1% of Japanese semaglutide recipients and 36.8% of placebo recipients, similar to overall trial rates of 62.9% and 34.3%.
Semaglutide numerically favored MASH resolution across BMI categories; in participants with BMI below 27 kg/m², rates were 57.1% with semaglutide and 26.7% with placebo.
Fibrosis improvement without worsening steatohepatitis occurred in 36.5% with semaglutide and 28.9% with placebo in the Japanese subgroup; the source notes that the treatment difference was imprecise in this small subgroup with a relatively high placebo response.
Japanese participants had a lower mean BMI than the overall population (29.8 vs 34.3 kg/m²), and 21.8% had BMI below 25 kg/m², compared with 6.7% overall. Percentage weight loss was 11.4% in Japanese participants versus 10.5% overall.
The source describes the safety profile as broadly consistent with the global trial and notes that subgroup analyses by BMI and age were exploratory; efficacy in non-obese participants with BMI below 25 kg/m² remains unestablished.

Clinical Implications

The subgroup findings support the applicability of the overall ESSENCE histologic results to the Japanese participants studied, including those with lower BMI, but do not establish efficacy specifically in non-obese patients with BMI below 25 kg/m². The source states that larger cohorts and extended follow-up are needed to confirm findings and determine whether treatment reduces liver-related events.

Conclusion

In this Japanese ESSENCE subgroup, semaglutide outcomes for MASH resolution and fibrosis improvement were broadly aligned with the overall trial population. The small subgroup and exploratory analyses limit conclusions for specific BMI and age groups.