A new potential treatment for fatty liver disease is making waves after initial results from a clinical trial showed that nearly two in three patients reduced liver fat and inflammation with weekly semaglutide injections over 18 months.

Published in the New England Journal of Medicine, the ongoing trial offers hope for millions battling Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD), a silent condition tied to diabetes and heart disease. This trial tested semaglutide in patients with advanced MASLD (F2 and F3 fibrosis). Results showed 62.9% of semaglutide-treated patients resolved liver inflammation without worsening fibrosis. Patients lost an average of 10.5% of body weight.

First Check spoke to Dr Rajiv Kovil, Head of Diabetology at Zandra Healthcare, Mumbai, who weighs in on the findings and the challenges ahead.

What is the significance of the ongoing clinical trials using semaglutide 2.4 mg weekly shots for one-and-a-half years to reduce fatty liver?

In the Phase 3 trials, 62.9% of patients treated with semaglutide experienced a resolution of steatohepatitis without any worsening of fibrosis, while 37% showed an actual improvement in fibrosis. These results are especially significant because MASLD is closely linked to a range of metabolic conditions, including type 2 diabetes and cardiovascular disease. A drug that can reverse liver fibrosis represents a major breakthrough—not just for individual patients, but for public health more broadly.

Already approved for weight loss, semaglutide targets MASLD through multiple mechanisms. It reduces appetite, lowers insulin resistance, decreases liver fat, and has anti-inflammatory effects—offering a comprehensive approach to managing this complex disease.

How does semaglutide work, and what are its weight loss benefits?

Semaglutide helps reduce liver fat primarily by promoting weight loss, lowering insulin resistance, and decreasing appetite. It also offers important metabolic benefits by reducing levels of glucagon, post-meal blood sugar, and triglycerides. Beyond these effects, semaglutide has anti-inflammatory properties that act through receptors in the brain, gut, and peripheral nervous system. These combined actions improve liver health—helping resolve inflammation and modestly improve fibrosis.

What treatments are available for MASLD?

Currently, the mainstay of treatment for MASLD involves lifestyle changes, especially achieving 7–10% weight loss through a Mediterranean diet and regular exercise. In certain cases, medications like pioglitazone and vitamin E are used.  Weight loss of 7–10% is most effective. Medications like pioglitazone and vitamin E work for biopsy-proven cases.

What are the challenges in treating MASLD?

An estimated 99% of MASLD patients remain undiagnosed, as the disease often progresses silently until advanced stages. Despite its strong links to obesity and diabetes, only one drug has been approved in the U.S., and diagnosis typically requires costly procedures like liver biopsies. A lack of public awareness and the challenge of maintaining long-term lifestyle changes further complicate effective management.

Also read: NAFLD in India: The Silent Epidemic Damaging Liver Health