Skip to main content

20-06-2024 | Non-Alcoholic Fatty Liver Disease | Editor's Choice | News

Tirzepatide shows promise for metabolic dysfunction-associated steatohepatitis

Author: Laura Cowen


medwireNews: Patients with metabolic dysfunction-associated steatohepatitis (MASH) and moderate or severe fibrosis have significantly higher rates of disease resolution, without worsening fibrosis, when given tirzepatide rather than placebo, show data from the phase 2 SYNERGY-NASH trial.

Rohit Loomba (University of California at San Diego, USA) and co-investigators explain that tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist that is known to “induce substantial weight reduction” in people with type 2 diabetes and/or obesity.

In addition, treatment with tirzepatide led to a reduction in liver fat and an improvement in biomarkers of MASH and fibrosis in a trial among people with type 2 diabetes, but its efficacy in people with MASH and moderate or severe fibrosis is unclear.

To investigate, Loomba and team randomly assigned 190 people with biopsy-confirmed MASH and moderate or severe (stage F2 or F3) fibrosis to receive once-weekly subcutaneous tirzepatide 5 mg (n=47), 10 mg (n=47), or 15 mg (n=48), or placebo (n=48) for 52 weeks. The participants had a mean age of 54.4 years and a mean BMI of 36.1 kg/m2. Over half (57%) were women and 58% had type 2 diabetes.

The researchers report in The New England Journal of Medicine that, at 52 weeks, participants given tirzepatide had significantly higher rates of MASH resolution without worsening of fibrosis than those given placebo. The rates were 44%, 56%, and 62% in the tirzepatide 5 mg, 10 mg, and 15 mg groups, respectively, compared with 10% in the placebo group.

In addition, people given tirzepatide 5 mg, 10 mg, and 15 mg were more likely to have an improvement of at least one fibrosis stage without worsening of MASH at 52 weeks than those given placebo, at rates of 55%, 51%, and 51%, respectively, versus 30%.

Loomba and co-authors comment: “The relatively short duration of the SYNERGY-NASH trial (52 weeks) may account for the similar incidence of improvement in fibrosis (51 to 55%) across the three doses of tirzepatide. Alternatively, fibrosis regression of approximately 50% may be the ceiling effect with weight reduction.”

Tirzepatide treatment was also associated with greater improvements in several secondary outcomes versus placebo including the overall nonalcoholic fatty liver disease activity score and its subscores for steatosis, lobular inflammation, and hepatocellular ballooning, as well as blood markers of liver injury.

Participants in the tirzepatide 5 mg, 10 mg, and 15 mg arms had a greater mean percentage reduction in bodyweight during the study than those in the placebo arm, at a respective 10.7%, 13.3%, and 15.6% versus 0.8%. Furthermore, Loomba et al say that “[t]here appeared to be an association between greater degrees of weight reduction and higher incidences of MASH resolution without worsening of fibrosis, but the relationship with weight reduction was less apparent for reduction in fibrosis without worsening of MASH.”

There were no unexpected adverse events (AEs) and those that did occur typically involved mild or moderate nausea, diarrhea, or constipation. Serious AEs occurred in 6% of participants given tirzepatide and 6% of those given placebo.

The researchers conclude: “Larger and longer trials are needed to further assess the efficacy and safety of tirzepatide for the treatment of MASH with liver fibrosis and to determine whether tirzepatide treatment could reduce the risk of major adverse liver outcomes.”

The study findings were simultaneously presented at the EASL Congress 2024 in Milan, Italy.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

N Engl J Med 2024; doi:10.1056/NEJMoa2401943
EASL Congress 2024; Milan, Italy: 6–8 June


Related topics

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Webinar | 06-02-2024 | 20:00 (CET)

Mastering chronic pancreatitis pain: A multidisciplinary approach and practical solutions

Severe pain is the most common symptom of chronic pancreatitis. In this webinar, experts share the latest insights in pain management for chronic pancreatitis patients. Experts from a range of disciplines discuss pertinent cases and provide practical suggestions for use within clinical practice.

Sponsored by: Viatris

Developed by: Springer Healthcare
Live Webinar | 01-10-2024 | 12:30 (CEST)

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

Live: Tuesday 1st October 2024, 12:30-14:00 (CEST)

In this live webinar, Professor Martin Dreyling and an esteemed, international panel of CAR-T experts will discuss the very latest data on the safety, efficacy and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL, as presented at ASH 2023, EU CAR-T 2024, and EHA 2024. 

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Sponsored by: Novartis Pharma AG

Chaired by: Prof. Martin Dreyling
Developed by: Springer Healthcare