ESSENCE: semaglutide for MASH liver disease, 72-week interim results

Why this study matters

MASH (metabolic dysfunction-associated steatohepatitis, previously called NASH) is fatty liver disease with inflammation that can scar the liver. It is closely tied to higher body weight and type 2 diabetes. An earlier phase 2 trial found that daily semaglutide (Wegovy, Ozempic) resolved MASH but did not clearly improve scarring. ESSENCE is the large phase 3 trial that tested the weekly 2.4 mg dose used for weight management, and unlike the earlier trial it showed a benefit on scarring. Canadian readers living with both a higher body weight and fatty liver disease are likely to hear about it.

Who was in the study

The full trial randomized 1,197 adults with MASH confirmed by liver biopsy (a small tissue sample) and fibrosis stage 2 or 3. Fibrosis stages run from F0 (no scarring) to F4 (cirrhosis), so these people had moderate to advanced scarring but not cirrhosis.

This paper reports a planned interim analysis at week 72 involving the first 800 participants: 534 on semaglutide and 266 on placebo. The trial is ongoing and planned to last 240 weeks. It is multicentre, meaning it ran at many sites. The summary we reviewed does not list the countries.

What the researchers did

This is a phase 3, randomized, double-blind, placebo-controlled trial. Randomized means chance decided the treatment, in a 2:1 ratio. Double-blind means neither participants nor staff knew who was on the medicine. Placebo means an inactive injection that looked the same. Phase 3 means a large trial designed to confirm benefit and safety.

People injected semaglutide 2.4 mg or placebo under the skin once a week. Part 1 of the trial had two main outcomes, both judged on a repeat biopsy at week 72: resolution of steatohepatitis (MASH) with no worsening of fibrosis, and a reduction in fibrosis with no worsening of steatohepatitis.

What they found

Both main outcomes favoured semaglutide (R32-C17, R32-C18).

A confidence interval (CI) is the range where the true difference most likely sits. All four results were very unlikely to be chance (P less than 0.001). The combined outcome and body weight were secondary outcomes that were included in the plan to adjust for multiple testing, which makes them more reliable than unplanned findings.

Mean changes in bodily pain scores did not differ significantly between groups.

Side effects and people who stopped

Stomach and gut side effects were more common in the semaglutide group. The summary we reviewed does not report the percentages, how many people stopped treatment, or how many stopped because of side effects.

What this study does not tell you

• This is a planned interim analysis of 800 of 1,197 people at 72 weeks. Final results at 240 weeks are still to come.
• Biopsy changes are a marker. The trial has not yet shown whether people avoid liver failure, transplant or death over the long term.
• Everyone had F2 or F3 fibrosis. A separate small trial in people with cirrhosis did not show a benefit, so this result does not extend to cirrhosis.
• Side effect and discontinuation figures were not in the summary we reviewed.
• The results cannot be compared directly with the earlier phase 2 trial, which used daily doses and a different population.
• The trial is funded by the maker of semaglutide, and our data extraction relied on the abstract only.

What it means in Canada

ESSENCE is the largest randomized evidence so far that weekly semaglutide 2.4 mg can improve the liver itself in people with MASH and moderate to advanced scarring. Whether it is used or covered for this purpose in Canada is a separate question. See semaglutide in Canada and public drug coverage by province.

Related reading

Other studies in this library that bear on the same question.

Source