‘Unequivocally yes’: MASH therapies still needed despite boom in GLP-1 use in liver disease
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Although use of glucagon-like peptide-1 agonists for diabetes and weight loss has soared with indications now expanding into liver diseases, specifically metabolic dysfunction-associated steatohepatitis, the jury is still out on its benefit.
With the recent FDA approval of Rezdiffra (resmetirom, Madrigal Pharmaceuticals) for the treatment for MASH, the question is whether (and how) GLP-1s will fit in the treatment pipeline for this disease.
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“With the advent of GLP-based therapies, do we need to develop drugs for MASH? The answer is unequivocally yes,” the late Stephen A. Harrison, MD, who provided the idea for this story, previously told Healio Gastroenterology. “These drugs do not impact fibrosis to any significant degree — if they do, they take forever to get there. The market penetration of GLP-1s is going to be about 30%. It’s a big topic and physicians want to know: Do I really need to focus on these?”
The lack of improvement in fibrosis with GLP-1s was demonstrated in a 2020 study published in The New England Journal of Medicine, in which patients with MASH and stage 2 or 3 fibrosis were randomly assigned to once-daily semaglutide (Ozempic, Wegovy; Novo Nordisk) 0.1 mg, 0.2 mg or 0.4 mg or placebo. While a significantly greater percentage of patients on semaglutide achieved MASH resolution with no worsening of fibrosis compared with placebo, there was no difference in improvement of fibrosis stage between treatment and placebo groups. As such, more data are needed to understand the benefits of GLP-1s in MASH.
In this month’s Healio Gastroenterology Exclusive, two hepatologists and two endocrinologists provide perspectives on the use of GLP-1s for the treatment of MASH, while Zobair M. Younossi, MD, MPH, shares his insights in a guest editorial.
Healio Gastroenterology thanks Rita Basu, MD, Scott Isaacs, MD, FACP, FACE, Rohit Loomba, MD, MHSc, and Arul Sanyal, MD, for their views into how the fields of hepatology and endocrinology are tackling the use of GLP-1s for the treatment of patients with MASH and/or obesity and type 2 diabetes.
Read more on each of their perspectives below:
Editor’s note: The discussion with Dr. Harrison took place prior to his passing on April 23.
- Reference:
- Newsome PN, et al. N Eng J Med. 2020;doi:10.1056/NEJMoa2028395.
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