Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) (formerly called fatty liver disease or NASH) is extremely common, affecting about 1 in 4 adults globally. In people with obesity, about 75% have MASLD, and about 1 in 3 have MASH. In people with elevated weight, MASLD/MASH can improve with weight loss.

Today’s question is: can GLP1-based weight loss medications benefit liver health in people with MASH?

The short answer to this question is – YES! In our recently published 2025 Obesity Canada Pharmacotherapy Clinical Practice Guidelines, we recommend GLP-1 based obesity pharmacotherapy for people with MASH, for weight loss and improvement in MASH – with the strongest data for semaglutide 2.4mg weekly (Wegovy), and also with data for tirzepatide (Zepbound/Mounjaro) and liraglutide (Saxenda, but studied at a lower dose) (disclosure: I am the lead author of these Guidelines). Let’s dig into the details!

As a backgrounder, there are two types of improvements that we are looking for: improvement in MASH (inflammation), and regression of fibrosis (scarring). Regression of fibrosis is especially important, because fibrosis is associated with risk of progression to liver cirrhosis, liver decompensation, liver cancer, and liver-related mortality. In other words, improving fibrosis can favorably alter the natural history of MASH and improve long term outcomes.

The ESSENCE study is an ongoing phase 3 study of semaglutide 2.4mg weekly (Wegovy) vs placebo in nearly 1200 people with MASH and fibrosis stage 2 or 3 (moderate to severe liver scarring). The results of part 1 of this study were published in the New England Journal of Medicine, which was a planned interim analysis of the first 800 people in the study conducted at week 72. This study demostrated resolution of MASH without worsening of fibrosis in 62.9% of people with semaglutide vs 34.3% with placebo. A reduction in fibrosis without worsening of MASH was seen in 36.8% of people in the semaglutide group vs 22.4% with placebo. Weight decreased by 10.5% in the semaglutide group vs 2% with placebo. Part 2 of the study (still ongoing) will assess effects on cirrhosis-free survival after 240 weeks of follow up. Based on these data, Wegovy is the first and only GLP1 medication approved (in USA) for treatment of MASH. The only other medication ever approved for treatment of MASH (in USA) is resmetirom, which does not cause weight loss (blogged here).

Tirzepatide (Mounjaro/Zepbound) has also been shown to benefit liver health in people with MASH. The SYNERGY-NASH study was a smaller and shorter phase 2 study of 190 people with BMI 27-50 kg/m2 and MASH with stage F2 or F3 (moderate to severe) fibrosis. At 52 weeks, they found resolution of MASH without worsening of fibrosis in 44%, 56% and 62% with tirzepatide 5mg, 10mg, 15mg weekly vs 10% with placebo. They also found a reduction in fibrosis without worsening of MASH in 55%, 51%, and 51% with tirzepatide 5/10/15mg vs 30% with placebo. These phase 2 data are not enough for approval of tirzepatide as a MASH treatment – a longer, larger phase 3 trial would be required to show benefit.

Liraglutide (Saxenda) at a lower dose (1.8mg daily) than the approved Saxenda weight management dose (3mg) showed benefit to induce resolution of MASH without worsening of fibrosis in 39% of people with liraglutide vs 9% with placebo, in the small, phase 2, 48 week LEAN study of 52 people with MASH and BMI of at least 25.

In all of these studies, side effects seen were predominantly gastrointestinal in nature, in keeping with what we know of the GLP1 medication class.

BOTTOM LINE: GLP1 based medications demonstrate benefit to improve MASH liver disease. With the first phase 3 data now published with semaglutide 2.4mg (Wegovy), hopefully this will pave the way toward further approvals and financial coverage of treatment for people living with MASH.

Disclaimer: I volunteered my time and received no remuneration for writing this Guidelines chapter. I am/have been an investigator in clinical trials of liraglutide, semaglutide, and tirzepatide. I receive honoraria as a continuing medical education speaker and consultant from the makers of semaglutide and liraglutide (Novo Nordisk), and tirzepatide (Eli Lilly).

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