A common liver disease is quietly affecting millions of Americans. Are we doing enough to catch it early?
In this episode, TRC Healthcare Associate Editor and Clinical Pharmacist Sara Klockars, PharmD, explores the growing prevalence of MASLD and MASH. She reviews newly approved treatment options, including semaglutide and resmetirom, and discusses how healthcare teams can help identify, support, and manage patients throughout their care journey.
This is an excerpt from our April 2026 Pharmacy Essential Updates continuing education webinar series.
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TRC Healthcare offers CE credit for this podcast for pharmacist subscribers at our platinum level or higher and pharmacy technician subscribers. Log in to your Pharmacist’s Letter or Pharmacy Technician’s Letter account and look for the title of this podcast in the list of available CE courses. None of the speakers have anything to disclose.
Clinical Resources from Pharmacist’s Letter, Pharmacy Technician’s Letter, and Prescriber Insights:
- Article: Know the Latest MASH Treatment Options
- Chart: Comparison of Drugs for Metabolic Liver Disease
- Chart: GLP-1 and GIP/GLP-1 Receptor Agonist Interactive Comparison Chart
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Transcript:
This transcript is automatically generated.
00:00:04 Narrator
Welcome to Clinical Capsules from TRC Healthcare, your trusted source for practical, evidence-based updates.
00:00:11 Narrator
On this episode, Associate Editor and Clinical Pharmacist Sara Klockars breaks down what pharmacy teams need to know about MASLD and MASH, including the latest evidence on semaglutide and resmetirom, along with key opportunities to support patients throughout their treatment journey in an excerpt from our popular Pharmacy Essential Updates webinar series.
00:00:32 Narrator
This podcast offers Continuing Education credit for pharmacists and pharmacy technicians.
00:00:37 Narrator
Please log in to your Pharmacist’s Letter or Pharmacy Technician’s Letter account and look for the title of this podcast in the list of available CE courses.
00:00:45 Narrator
None of the speakers have anything to disclose.
00:00:49 Narrator
Catch new episodes of Clinical Capsules every 2nd and 4th Tuesday, bringing concise, actionable insights from TRC experts straight to your ears.
00:00:58 Narrator
With that, let’s get started.
00:01:00 Sara Klockars
We’re talking about this since injectable semaglutide, Wegovy, is the first GLP-1 agonist approved for certain patients with MASH.
00:01:17 Sara Klockars
And before we dig in more, let’s just review the spectrum of metabolic dysfunction-associated steatotic liver disease. This will come into play when we talk about treatment options.
00:01:29 Sara Klockars
This is when there’s excess fat in the liver in a person with at least one metabolic risk factor, such as insulin resistance or diabetes, high cholesterol, obesity, and that can cause fat creation in the liver or that steatotic liver disease or fatty liver disease.
00:01:47 Sara Klockars
And then if it’s left untreated, the disease progresses. And then we have metabolic dysfunction-associated steatohepatitis or MASH.
00:01:57 Sara Klockars
And this is when the fat buildup leads to inflammation and damage to the liver cells.
00:02:02 Sara Klockars
And then it can progress to fibrosis, or this is when scar tissue starts to replace normal tissue in the liver, and eventually can progress to cirrhosis when scarring is extensive or severe, and it usually can’t be reversed. Or it can also lead to liver cancer.
00:02:22 Sara Klockars
So you can see why it’s important to try to find it early and to treat this early.
00:02:30 Sara Klockars
And we’re hearing more about metabolic dysfunction-associated steatotic liver disease because it’s a leading cause of chronic liver disease.
00:02:39 Sara Klockars
In fact, about one in four adults in the US have MASLD and about 15 million adults in the US have MASH.
00:02:48 Sara Klockars
So it’s important to note that the prevalence is rising.
00:02:53 Sara Klockars
And this increase goes hand in hand with increases in the metabolic risk factors.
00:02:58 Sara Klockars
But many may not know they have this since patients with MASH usually do not have symptoms. And we rely on screening when patients have these risk factors.
00:03:08 Sara Klockars
So diabetes and obesity seem to have the most impact on the history of MASLD and progression to MASH.
00:03:16 Sara Klockars
Some other risk factors include high cholesterol, high blood pressure, smoking, postmenopausal women, and males over age 50 years.
00:03:27 Sara Klockars
When it comes to managing patients with MASLD, lifestyle changes and controlling comorbidities are key for all patients.
00:03:35 Sara Klockars
So weight loss is the most important treatment.
00:03:38 Sara Klockars
Losing over 5% of body weight reduces liver fat.
00:03:42 Sara Klockars
Losing over 10% can lead to MASH resolution and reducing that liver fibrosis or scarring.
00:03:49 Sara Klockars
So those weight loss strategies, healthy eating, physical activity, those are the cornerstone of managing MASLD.
00:03:57 Sara Klockars
And then beyond weight loss, we want to advise limiting alcohol since alcohol can worsen liver damage. Advise smoking cessation since smoking is a risk factor for MASLD.
00:04:11 Sara Klockars
And also because of those metabolic conditions, the diabetes, high cholesterol, high blood pressure go hand in hand with fatty liver disease, it’s important to optimize meds for these conditions.
00:04:23 Sara Klockars
So one example, we want to continue to recommend statins to reduce cardiovascular risk in patients with high cholesterol and MASLD.
00:04:34 Sara Klockars
But you might be wondering if statins are safe to use in patients with this type of metabolic liver disease, and they are.
00:04:41 Sara Klockars
In fact, some data suggests potential benefits of statin therapy in patients with stable liver disease, including MASLD.
00:04:50 Sara Klockars
So optimizing the treatment of these comorbidities is key before considering MASH-specific medications.
00:05:00 Sara Klockars
And as I mentioned earlier, we now have injectable semaglutide or Wegovy, and we also have resmetirom or Rezdiffra as these two FDA-approved options to reduce that liver fat and inflammation when lifestyle changes and weight reduction aren’t enough.
00:05:17 Sara Klockars
We don’t have good evidence yet that these meds reduce risk of cirrhosis or liver transplant yet.
00:05:24 Sara Klockars
We may see one of these meds used for noncirrhotic MASH with moderate to advanced liver fibrosis, stage F2 to F3 fibrosis, along with a healthy diet and exercise.
00:05:37 Sara Klockars
So what does that mean?
00:05:40 Sara Klockars
So jumping back to the progression of MASLD, these meds are for a more advanced form of MASH when patients have scar tissue or fibrosis, but yet not for cirrhosis.
00:05:52 Sara Klockars
So this is usually diagnosed by specialists with the use of different risk calculators, special ultrasounds, or imagings of the liver, and in some cases, a liver biopsy to look more closely at those liver cells.
00:06:06 Sara Klockars
Liver function tests can be used as a marker, but not for diagnosis.
00:06:10 Sara Klockars
So for example, liver function tests can be normal in patients with MASH.
00:06:18 Sara Klockars
So honing in a bit more, there are different stages of fibrosis.
00:06:23 Sara Klockars
So F0 is no fibrosis, all the way up to F4, which is cirrhosis and extensive scarring.
00:06:31 Sara Klockars
And these stages come into play since these meds are specifically for stage F2 or F3.
00:06:39 Sara Klockars
And this will be important if you handle prior auths.
00:06:44 Sara Klockars
So if a MASH-specific med is needed, expect most patients to get injectable semaglutide, especially if the patient has another indication for a GLP-1 agonist such as obesity.
00:06:57 Sara Klockars
And when injectable semaglutide is used for MASH, patients will start at that dose of 0.25 milligrams once weekly.
00:07:05 Sara Klockars
Increase monthly as tolerated to that target dose of 2.4 milligrams once weekly.
00:07:14 Sara Klockars
And just a quick note that the injectable Wegovy HD or high dose of 7.2 milligrams that’s been approved is for weight reduction in adults.
00:07:26 Sara Klockars
So when you get a prescription for injectable semaglutide, enter directions correctly, double checking those strengths and SIGs when calculating days supply and filling prescriptions.
00:07:37 Sara Klockars
And also ask about the indication for these products just to double check you have the right med since there’s also injectable semaglutide for diabetes.
00:07:47 Sara Klockars
Don’t automatically substitute oral Wegovy for injectable Wegovy. They’re not considered equivalent. And other semaglutide dosage forms aren’t approved for MASH.
00:07:58 Sara Klockars
When it comes to efficacy, injectable semaglutide once a week for 72 weeks with diet and exercise leads to MASH resolution, which was defined as minimal to no liver inflammation or cell injury, in about one of four patients treated versus placebo.
00:08:16 Sara Klockars
Plus, about one in seven patients have fibrosis improvement.
00:08:22 Sara Klockars
And as we know with GLP-1 agonists, GI side effects are common, so that nausea, vomiting, diarrhea, and these can usually improve over time.
00:08:32 Sara Klockars
There are some strategies we can share with our patients to set them up for success, such as reinforcing the need to start at that low dose, slowly increase the dose.
00:08:41 Sara Klockars
We can slow the titration if side effects are too severe.
00:08:45 Sara Klockars
And as pharmacists, we can counsel patients on adjusting their meals. So for example, advise eating smaller meals more slowly, and to stop eating before they’re full.
00:08:58 Sara Klockars
And it’s also a good reminder that these meds, along with rapid weight loss, may lead to gallbladder problems, so patients should report severe stomach pain right away.
00:09:08 Sara Klockars
And then moving along, we also have resmetirom, which activates thyroid hormone receptor beta, which is a major form of thyroid hormone receptor in the liver.
00:09:19 Sara Klockars
By doing this, it’s thought to increase the metabolism or breakdown of that liver fat and then reduce fatty acid and triglyceride formation and buildup in the liver.
00:09:32 Sara Klockars
Resmetirom is dosed based on actual body weight, usually 80 or 100 milligrams once daily.
00:09:38 Sara Klockars
There’s also a 60 milligram dose that may be needed for dose adjustments due to drug interactions.
00:09:45 Sara Klockars
And then it’s a specialty med available via limited distribution and costs about $4,200 a month.
00:09:52 Sara Klockars
So expect prior auths if you dispense this.
00:09:57 Sara Klockars
And when it comes to efficacy, oral resmetirom daily for 12 months with diet and exercise leads to MASH resolution in about one in six patients treated versus placebo.
00:10:08 Sara Klockars
Plus about one in 10 patients have fibrosis improvement.
00:10:13 Sara Klockars
And there are some other things to consider for patients using resmetirom. It has many interactions, so pay close attention to the interaction warnings if you dispense this.
00:10:23 Sara Klockars
For example, as I mentioned earlier, we want to treat comorbidities, which often include high cholesterol, so patients are often on statins.
00:10:32 Sara Klockars
But resmetirom can increase concentrations of some statins in the blood.
00:10:38 Sara Klockars
So if a patient’s getting a new prescription for resmetirom, we may need to recommend a lower statin dose.
00:10:44 Sara Klockars
For patients taking resmetirom, we’d want to limit rosuvastatin or simvastatin to a max of 20 milligrams a day and pravastatin or atorvastatin to a max of 40 milligrams per day.
00:10:58 Sara Klockars
We also want to caution about common side effects, diarrhea, nausea, itching.
00:11:02 Sara Klockars
We also think of resmetirom as helping liver function in patients with MASH, but it can also cause liver injury.
00:11:11 Sara Klockars
So patients will need baseline and follow-up liver function monitoring, which is likely typical for patients with MASH, and then tell patients to promptly report severe GI pain, which can be a red flag for rare gallbladder problems that can happen with resmetirom as well.
00:11:28 Sara Klockars
But before we move on to other meds, I just want to note that resmetirom hasn’t been directly compared to injectable semaglutide.
00:11:36 Sara Klockars
We also don’t have good evidence on using these two approved meds in combination for MASH yet.
00:11:42 Sara Klockars
It’s intriguing since these two meds have very different mechanisms of action.
00:11:47 Sara Klockars
Plus some patients in the phase three resmetirom trials were on GLP-1 agonists, and the secondary analysis showed similar results in all of these patients, so the patients using both didn’t fare any better.
00:12:01 Sara Klockars
In addition, the combination may not be covered by some payers, but the landscape in MASH treatment is changing rapidly.
00:12:11 Sara Klockars
And I want to touch on a few other options you may see.
00:12:14 Sara Klockars
Oral pioglitazone or Actos may lead to MASH resolution in about one of four patients and may slow fibrosis progression.
00:12:22 Sara Klockars
Studies are small but have consistently shown improvement.
00:12:27 Sara Klockars
In fact, the American Diabetes Association recommends pioglitazone either alone or with a GLP-1 receptor agonist for patients with type 2 diabetes and MASH.
00:12:40 Sara Klockars
But keep in mind the risks of pioglitazone, modest weight gain, fluid retention, potential heart failure exacerbations.
00:12:48 Sara Klockars
So just keep that in mind.
00:12:51 Sara Klockars
And then vitamin E has gotten some buzz over the years.
00:12:55 Sara Klockars
But there’s limited evidence it may reduce liver fat in patients without diabetes.
00:13:01 Sara Klockars
Plus some evidence suggests vitamin E is linked with bleeding, prostate cancer, stroke, and other risks.
00:13:08 Sara Klockars
So vitamin E has really fallen out of favor with these newer options.
00:13:15 Sara Klockars
And then we have many other promising meds, including other GLP-1 agonists.
00:13:21 Sara Klockars
For instance, one phase two trial suggests tirzepatide 15 milligrams a week leads to MASH resolution in about one of every two patients treated for 52 weeks compared to placebo.
00:13:34 Sara Klockars
Many other GLP-1 agonists are in the pipeline that appear to be very effective.
00:13:40 Sara Klockars
Plus, there’s some evidence to suggest the SGLT2 inhibitors may reduce liver fat in patients with type 2 diabetes.
00:13:48 Sara Klockars
In addition, many meds with new mechanisms, such as fibroblast growth factor 21 analogs, are in phase 3 trials.
00:13:58 Sara Klockars
So stay tuned.
00:14:02 Sara Klockars
And let’s chat quickly before we wrap up about what else we can do in our pharmacies since so many patients we see every day have metabolic risk factors for MASH.
00:14:13 Sara Klockars
In addition to reinforcing those lifestyle changes, we can help keep med lists current, asking about meds from other pharmacies or delivered to the house.
00:14:23 Sara Klockars
This can also help us see if patients are on statins or blood pressure medicines, refilling them regularly, and we can help try to optimize the treatment of those risky comorbidities.
00:14:37 Sara Klockars
And since we have so many GLP-1 agonists and they’re used for many different indications, we definitely need to stay alert for duplicate therapies.
00:14:46 Sara Klockars
For example, a patient may receive semaglutide from a liver specialist for MASH, but maybe they’re on tirzepatide from their primary care clinician for diabetes.
00:14:55 Sara Klockars
So we would want to alert the pharmacist to this combination.
00:15:00 Sara Klockars
And we can also continue to help with prior auths for these medications.
00:15:04 Sara Klockars
For instance, semaglutide and resmetirom usually need to be prescribed by or in consultation with a specialist such as a gastroenterologist or hepatologist.
00:15:11 Sara Klockars
And we may need to track down some info to confirm that F2 or F3 fibrosis diagnosis.
00:15:27 Sara Klockars
Keep in mind that even though some of these other medications have evidence for MASH, they may not be covered unless the patient is using it for an approved indication.
00:15:38 Sara Klockars
We’ve also got lots of resources for you. You can print our one-page comparison of drugs for metabolic liver disease to have as a quick reference.
00:15:46 Sara Klockars
And we have many GLP-1 agonist resources as well to help you keep these meds straight.
00:15:51 Sara Klockars
You can use our interactive comparison chart to sort through products, indications, clinical outcomes, and more.
00:16:01 Narrator
Thanks for listening.
00:16:02 Narrator
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00:16:06 Narrator
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00:16:10 Narrator
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00:16:18 Narrator
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00:16:23 Narrator
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00:17:04 Narrator
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