Semaglutide provides liver health benefits in menopausal women with MASH: Insights from the ESSENCE trial

touchENDOCRINOLOGY coverage of EASL 2026

Women in menopause with MASH are known to have a higher risk of advanced fibrosis and faster disease progression. Could you outline the clinical burden in this population and explain the unmet needs in its management?

The clinical burden of MASH in and of itself is pretty extensive. Approximately 30% of the population has steatotic liver disease, and around 6–8% will develop the progressive form, steatohepatitis. We have known for some time that estrogen is protective and that premenopausal women tend to have milder disease than postmenopausal women. We also know that, as women age, their risk of fibrosis progression becomes comparable to what we see in men.

One of the unanswered questions in the field has been whether there is a differential response to treatment as women progress through menopause, given the higher burden of fibrosis progression in this patient population.

Could you describe the rationale for conducting this post hoc analysis of the ESSENCE trial, and explain how menopause status was defined and incorporated into the study design?

The ESSENCE trial was a randomized, double-blind, placebo-controlled study evaluating the role of semaglutide therapy in patients with at-risk, clinically significant MASH, meaning they had definite steatohepatitis with fibrosis stage 2 or 3. The study demonstrated a treatment effect of semaglutide versus placebo in patients with biopsy-proven MASH after 72 weeks.

The purpose of this post hoc analysis was to evaluate whether menopause had an impact on treatment response by comparing postmenopausal women with premenopausal women and men. This will help us tailor therapeutics more effectively, ensuring the right treatment is given at the right time to the right patient.

It is important to understand whether menopause influences treatment response, and that was the rationale behind conducting this analysis.

What were the key findings in terms of liver histology and non-invasive tests at week 72, and were there any notable differences in treatment response between women in menopause, women in premenopause, and male participants?

Interestingly, semaglutide did not demonstrate any differential treatment response between premenopausal women, postmenopausal women and men. In other words, the efficacy of this therapy for steatohepatitis in patients with fibrosis stage 2 or 3 was not influenced by age, sex or menopausal status, which was an exciting finding.

This suggests that semaglutide has broad applicability and utility in patients with MASH, regardless of menopausal status. The consistency of response across these groups provides reassurance that patients can derive meaningful liver-related benefits from treatment independent of these demographic factors.

These findings suggest that menopause does not reduce the likelihood of achieving liver health improvements with semaglutide. What do these results tell us about the role of semaglutide across different patient subgroups in MASH?

I think the results suggest that semaglutide has broad utility across all cohorts of patients with steatohepatitis, independent of these variables, and that the appropriate target population includes anyone with metabolic dysfunction and steatohepatitis.

The definition of metabolic dysfunction-associated steatotic liver disease is the presence of hepatic steatosis together with at least one cardiometabolic risk factor. So I think practitioners and clinicians can be largely agnostic to these other co-factors when deciding on a treatment plan for their patients. These findings support semaglutide as a foundational treatment for steatohepatitis, with benefits that appear consistent across different patient subgroups.

What questions remain unanswered regarding treatment outcomes in women in menopause with MASH, and what further analyses or studies are planned to better understand long-term clinical benefit?

I think across the therapeutic landscape of MASH, we see both responders and non-responders. One of the key questions that remains unanswered is why some patients do not respond. What is different about them compared with those who do respond?

We’ve learned from this analysis that, when patients achieve a response with semaglutide, that response is effective regardless of age, sex or menopausal status. However, we have not yet fully evaluated those patients who did not achieve the same response within the same timeframe. The question is: why? We have a lot of work ahead to better understand the factors that drive non-response.

In addition, how hormone-related changes influence the biology of the disease remains an important area of investigation. We have known for some time that premenopausal women appear to be protected against fibrosis progression, but why? What exactly is happening with hormone status that affects disease biology and contributes to fibrosis progression?

These questions warrant further study so that we can better understand the underlying mechanisms, tailor therapies more appropriately and ultimately individualize treatment plans based on where patients are in their life course.