- Semaglutide is a GLP-1 agonist medication that can assist with diabetes management and weight loss.
- Experts are interested in understanding additional potential health benefits of semaglutide.
- One study found that semaglutide helps to improve liver health in people with metabolic dysfunction-associated steatohepatitis, a serious form of fatty liver disease.
The use of
Experts are also interested in other uses of semaglutide. A recent study published in The New England Journal of Medicine furthered research on semaglutide, exploring how the drug affected outcomes for people with metabolic dysfunction-associated steatohepatitis, a type of liver disease.
The results suggest that semaglutide may help resolve steatohepatitis and decrease fibrosis.
This research was a phase 3 clinical trial involving people with metabolic dysfunction-associated steatohepatitis (MASH). As described in this study, MASH is a severe type of what used to be called nonalcoholic fatty liver disease.
The study also notes that MASH involves damage to liver cells, inflammation, and steatosis or fat buildup in the liver. Steatohepatitis, which involves fat buildup and inflammation in the liver, can then contribute to tissue scarring or fibrosis.
This study involved participants from hundreds of clinical sites in thirty-seven countries. The current published results report the end of the first part of the trial.
Among the participants, 534 received semaglutide, and 266 received a placebo. The research reported in this study lasted 72 weeks. Participants received 2.4mg injections of semaglutide each week, and they followed a 16-week dose escalation schedule.
All participants were at least 18 years old and had steatohepatitis and fibrosis. Researchers excluded participants who had other chronic liver problems besides nonalcoholic fatty liver disease. Other exclusion criteria included components like alcohol consumption over a certain amount and use of GLP-1 receptor agonists in the three months leading up to screening. All participants also received standard care for MASH. Participants got two liver biopsies to help evaluate the effects of semaglutide.
About 56% of participants had type 2 diabetes, and about 73% had obesity.
The researchers evaluated participants for two main outcomes: resolution of steatohepatitis, where liver fibrosis didn’t get worse, and improved fibrosis, where steatohepatitis did not get any worse. Researchers also evaluated participants for weight changes, pain, adverse events, and labs.
Semaglutide appeared to benefit participants more than the placebo. Almost 63% of participants who received semaglutide had steatohepatitis resolution without their fibrosis getting worse. Only 34.3% of participants in the placebo group experienced this outcome.
Additionally, 36.8% of participants who received semaglutide experienced decreases in liver fibrosis without their steatohepatitis getting worse, compared to 22.4% in the placebo group. Results were similar in sensitivity analyses that considered components like age, diabetes, and how bad fibrosis was.
Additionally, some participants experienced steatohepatitis resolution and decreased fibrosis. About 33% of the semaglutide group experienced this compared to about 16% in the placebo group.
Semaglutide’s effects on weight loss, inflammation, and pain
The semaglutide group also experienced an average 10.5% decrease in body weight compared to only an average 2% decrease in the placebo group. While it did not reach statistical significance, participants taking semaglutide also appeared to experience pain decreases more than the placebo group.
Participants in the semaglutide group had better outcomes from non-invasive testing as well. For example, more participants taking semaglutide experienced decreased enhanced liver fibrosis scores and decreased liver stiffness than participants on the placebo.
Other outcomes were better in the semaglutide group, too, such as greater decreases in systemic inflammation and cholesterol, as well as better insulin sensitivity.
Around 86% of participants in the semaglutide group reported an adverse event, compared to about 80% in the placebo group. The semaglutide group also experienced more gastrointestinal events, like nausea and constipation, than the placebo group. However, researchers found that “no new or liver-related safety signals emerged.”
Overall, the results of this study indicate that semaglutide may help improve liver outcomes for people with MASH. However, it does have limitations.
First, the research only included a small number of Black participants, as well as a low number of lean participants. There may be a need for more diversity in future research, and it’s unclear how the use of semaglutide benefits lean individuals with MASH. Researchers did not have data on biomarkers for alcohol consumption. They also acknowledge that genetic variations are part of what determines how someone responds to treatment.
This particular trial is ongoing and will have additional follow-up that will focus on cirrhosis-free survival. Thus, researchers did not share some information about clinical outcomes in this paper for reasons of study integrity. This part of the study included 800 randomized participants, and this did not have to do with how well participants were following taking semaglutide or the placebo or certain medication changes. Additionally, there was some missing data.
Researchers acknowledge that semaglutide helped to address problems of metabolic dysfunction that drive liver problems and holistically helped address “liver disease and associated cardiometabolic illness.”
It’s possible that the findings of this research are the result of weight loss. Mir Ali, MD, board certified general surgeon, bariatric surgeon, and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who was not involved in the study, noted the following to Medical News Today:
“This study showed a reduction of MASH with semaglutide use; however, because the greatest contributor to MASH is obesity, I believe this is more a function of weight loss than a direct effect of the medication. We see significant improvement in MASH in our surgical weight loss patients, and it seems to be directly related to the amount of weight lost. The clinical implications are that this shows another benefit to weight loss associated with use of semaglutide.”
This research holds promise for helping people with MASH and suggests another potential benefit of semaglutide.
Ian Storch, DO, an osteopathic physician specializing in gastroenterology and internal medicine and an American Osteopathic Association member, who was also not involved in the study, explained to MNT:
“MASH (Metabolic Associated Hepatitis) is such an important disease, which didn’t get much attention in the past for two reasons, one being our deficiency in cost-effective noninvasive imaging modalities to assess fibrosis and the second being our lack of treatment modalities. The study in the NEJM showing possible benefits of semaglutide in MASH patients with advanced inflammation and fibrosis is another exciting advance in our efforts to conquer this indolent, but deadly disease.”
