How I Treat MASLD/MASH: Dr Sidney Barritt on Pharmacotherapy

Dr Barritt discusses how he approaches the treatment of MASLD and MASH, both with medical therapies and lifestyle adaptations. 

A. Sidney Barritt, MD, is professor of medicine and director of the Liver Center at the University of North Carolina at Chapel Hill.

Hello. My name is Sid Barrett and I'm a transplant hepatologist at the University of North Carolina where I'm professor of medicine and director of the UNC Liver Center. I have both a clinical and research interest in metabolic dysfunction-associated steatotic liver disease or MASLD. And I see a lot of patients with this entity.

When I see a patient, they come to me from a variety of different places. Some patients are already seen by a gastroenterologist and well-curated with a biopsy. And then other patients come to see me from community health centers with just perhaps abnormal liver tests or imaging with steatosis. When I encounter patients with a suspected diagnosis of MASLD to MASH, I first want to get an assessment of how bad their disease is. And disease severity, we stage by fibrosis. And often patients will come to me with data for FIB-4 in hand where we can see if they are at low risk for advanced fibrosis or if they're at high risk for advanced fibrosis.

I'm also fortunate too that I have vibration control transient elastography for fibrosis embedded in my clinic, so I can assess patients and do a secondary test to measure how much fibrosis the patient has and also get an assessment of hepatic steatosis as well too. When we talk about fibrosis staging, it goes from 0 if there's none to 4 if we think the patient has cirrhosis. And once I have this data in my hand, I can have a conversation with the patient about types of therapy that we may employ.

In our multidisciplinary MASLD clinic, we use both lifestyle intervention and pharmacotherapy as part of our therapy. All patients should undergo some sort of lifestyle counseling, and that should take place with professional advice from a nutritionist to debunk a lot of the nonsense that's out there on social media and other platforms. Patients can get professional advice about good nutrition, how much protein, how much fat, how much carbohydrate behavior.

In addition to other lifestyle interventions, we work with a behavioral therapist. Where behavioral therapy is important is that MASLD and MASH is often rooted in our behaviors, particularly our relationship with food. A behavioral therapist can help with motivation, help with adherence, but also dissect how food may be used as a coping mechanism in many of our patients who describe themselves as boredom eaters or emotional eaters or stress eaters.

If patients are found to have either stage 2 or stage 3 fibrosis, they may also be appropriate for pharmacotherapy. Over the last 18 months, 2 different medications have been approved by the FDA for the treatment of stage 2 or stage 3 MASH. The first, in March of 2024, was resmetirom. This is a thyroid hormone beta agonist that removes fat from the liver and cuts back on this pathway of fat to inflammation and fibrosis. In the MAESTRO 3 clinical trial series, approximately one-third of people who were on resmetirom for one year had a reduction in fibrosis of at least one stage.

The next medication that was FDA approved was approved by the FDA was in August of 2025, and this was a medication that was already on the market for diabetes and obesity. This is semaglutide, marketed as Ozempic for diabetes and Wegovy for obesity. The dose that was studied for MASH was the Wegovy dose or the higher dose. And in this study, over a 72-week period, approximately 40% of patients had a reduction in fibrosis. So both of these medications are now commercially available for the treatment of stage 2 or stage 3e MASH.

The question of which medication to use for which patient is often a matter of debate and really has to be individualized. Where semaglutide, a GLP-1 receptor agonist, can help with diabetes and obesity, there are no GLP-1 receptors in the liver, so much of the benefit of this medication is likely indirect and thus may take a little bit longer, hence the 72-week study that was done for this drug. If a patient has poorly controlled diabetes or significant obesity, a GLP-1 may be the right medication for that type of patient. Whereas if a patient doesn't have diabetes or perhaps their diabetes is already well-controlled, resmetirom may be a better medication. Frequently in my clinic, I see patients come to me already on a GLP-1, yet they still have stage 2 or stage 3 MASH. This is where combination therapy may be of benefit as well too. By using a medication like resmetirom, which has a direct effect on that steatosis and a secondary impact on LDL and other cholesterol, pairing this with a medication that also impacts diabetes and weight, we now are treating multiple factors of metabolic syndrome with a direct impact on the liver.

So in these patients already on a prevalent GLP-1 who still have stage 2 or stage 3 fibrosis, I will add on resmetirom to these patients. However, I don't start both medications at the exact same time because what I want to make sure of is one, can a patient respond to a single drug rather than falling into this trap of polypharmacy? And two, I want to make sure that a patient can tolerate both drugs too. Both medications have the potential for some side effects, mostly GI. With resmetirom approximately 15% of patients develop diarrhea. With a GLP-1 receptor agonist, you can see issues of nausea, vomiting, and sometimes constipation. But I want to make sure that a patient can tolerate these medications so I don't start them simultaneously. But both can be used, I think, once a patient is established.

When I follow patients on these medications, after I initiate resmetirom, I recheck LFTs in a time period between 1 to 3 months later. In the clinical trials, there is a small flip in some patients with their ALT, but clinically this has not looked to be significantly important. I'll see patients usually in follow-up at 3 to 6 months to make sure they continue to tolerate the medication and recheck their liver enzymes. I'll reassess their fibrosis at 52 weeks. If the patient's had an improvement in their fibrosis, depending if they drop from say stage 3 to stage 2, I'll continue this medication. What remains to be somewhat of a question is if the patient has dropped from stage 3 or stage 2 all the way down to stage 1, should the patient continue? In many cases, I will continue the patient on their medication, as I think this is what's helped them get to this stage and pulling the rug out from underneath them is likely not going to be best for their long-term therapy.

A similar story can be told with GLP-1 receptor agonists. If a patient has weight loss on the GLP-1, we know that stopping the drug can often result in gaining the weight back. Additionally, if a patient's on a GLP-1 for diabetes, stopping the drug can cause an increase in that hemoglobin A1C. So along those lines, stopping the drug once you've reached a fibrosis stage reduction may not make sense for the long-term therapy of that patient. However, both of these drugs are new to the market in terms of their priority use in MASLD and MASH. So this will be ongoing as we see longer term outcomes released from both of these clinical trial series and continued accrual of real world data in treating patients. All in all, continued lifestyle intervention remains important in case the patient achieves the insurance or loses insurance and is unable to get the medication.

So these lifestyle interventions remain the backbone of therapy in addition to pharmacotherapy that should be coming.