Rezdiffra and Weight Loss Medicines: Rivals or Partners in Treating MASH?

For years, weight loss has been a critical part of managing conditions like nonalcoholic steatohepatitis (NASH/MASH). With the approval of Rezdiffra (resmetirom), patients now have a treatment option that directly addresses liver fat accumulation and fibrosis.

Does Rezdiffra help with weight loss and what does this mean for the role of weight loss in MASH treatment? Here's everything you need to know.

The importance of weight loss in MASH treatment

Weight loss is an important element of the overall approach to managing MASH. Although this liver condition is often associated with diabetes and obesity, the relevance of weight loss in managing it applies to both lean and obese patients ¹.

It's indicated that losing 3-5% of your body weight can help reduce liver fat. An even bigger weight reduction (7-10%) can alleviate inflammation and liver scarring (fibrosis) ².

Therefore, losing weight will likely remain a part of your treatment plan. Even though a specific medicine for fatty liver with fibrosis is now available.

Does Rezdiffra help with weight loss?

No. Resmetirom is focused on reducing fat from the liver, but not from other body parts. Improving fat metabolism in the liver can have a positive effect on overall body fat reduction. However, this is a potential secondary benefit of resmetirom, rather than a main effect. That's why it's prescribed alongside a special diet and physical exercise ³.

What weight loss medicines can be used with resmetirom in MASH treatment?

To maximise the effect of MASH therapy, especially in patients where obesity is also present, weight loss medicines can be used together with Rezdiffra. For example, GLP-1 antagonists such as semaglutide, or GIP and GLP-1 antagonists such as tirzepatide.

The combined use of resmetirom and weight loss medicines can address metabolic issues, as well as liver fat and fibrosis ⁴.

As indicated by recent clinical trials, GLP-1 antagonists such as semaglutide may even have the potential to be stand-alone MASH treatments. However, we're not there yet, as no approvals have been given to semaglutide for this indication.

Wegovy as a treatment for MASH

According to a recent press release, Novo Nordisk will apply for FDA approval and EMA approval for Wegovy (semaglutide) as a treatment for metabolic dysfunction-associated steatohepatitis (MASH) ⁵. This intention is based on the results of the Phase 3 ESSENCE trial with semaglutide.

Some of the key findings were:

• After 72 weeks of follow-up, 37% of patients treated with semaglutide saw their liver scarring improve. The result for the placebo group was 22.5%;
• 63% of semaglutide patients saw their MASH resolve without scarring getting worse. In the placebo group, 34% of patients demonstrated this result ⁵.

If this result turns into an approval for Wegovy as a MASH treatment, it could be an option for MASH patients living with overweight and obesity.

Rezdiffra vs Wegovy

If Wegovy (semaglutide) gets approval for treating MASH, it's important to understand how it compares to Rezdiffra. Here are some differences:

• Mechanism of action. Semaglutide mimics GLP-1 to regulate glucose and appetite, while resmetirom activates THR-b to enhance liver fat metabolism;
• Liver fat reduction. While for resmetirom, the reduction of fat build-up in the liver is a direct effect, for semaglutide this is a secondary effect of the overall weight loss;
• Insulin sensitivity. While semaglutide improves insulin sensitivity via weight loss, resmetirom is not shown to have a direct effect on insulin sensitivity;
• Anti-inflammatory action. Resmetirom's anti-inflammatory action is direct, whereas for semaglutide that's an indirect effect of overall weight loss ⁶.

As you can see, the two medicines have a different approach to MASH treatment. It may be that they will be relevant for a different subset of the patient population. We'll know more on this as Wegovy's approval decision comes. This isn't expected before 2026.

Mounjaro (tirzepatide) as a treatment for MASH

Mounjaro's manufacturer, Eli Lilly, has also been studying the medicine in the context of fatty liver with fibrosis (MASH). While there's no plan for regulatory approval for this indication yet, here are some of the reported results of the Phase 2 NASH trial involving tirzepatide:

• After 52 weeks of treatment, 10% of patients in the placebo group had their MASH resolved without worsening of the fibrosis. In the groups treated with tirzepatide, the same result was achieved by:
• 44% of patients receiving 5 mg of tirzepatide;
• 56% of patients receiving 10 mg of tirzepatide;
• 62% of patients receiving 15 mg of tirzepatide ⁷.

These results point to a potential role tirzepatide could play as a treatment for MASH in the future. However, further data are needed before we're there.

How to get Rezdiffra and/or weight loss medicines before they're available?

Rezdiffra is a recently approved medicine and as such, it's not yet available in most countries. As for weight loss medicines (GLP-1 antagonists in particular), they tend to be affected by supply shortages around the world.

Does this mean you have to wait to start your treatment? No.

If you have MASH and your doctor believes you could benefit from Rezdiffra (and weight loss medicines), then you can directly buy and import the medicines. Even if they're not approved or available in your country yet. This is possible under a global regulation known as Named Patient Import.

To get immediate access to Rezdiffra, semaglutide, or tirzepatide, get in touch with our expert team.

Referencje:

1. MASLD/MASH and Weight Loss. GI&Hepatology News, Accessed 18 December 2024.
2. Nazario, Brunilda. Metabolic dysfunction-associated steatohepatitis (MASH): What to Know. WebMD, 27 November 2024.
3. Rezdiffra (resmetirom): Uses, Side Effects, Dosage & Reviews. GoodRx, Accessed 18 December 2024.
4. Resmetirom and GLP-1 agonists for MASH: complementary rather than exclusive. Gut and Liver, Accessed 18 December 2024.
5. Fidler, Ben. Novo, with new results, to seek approval for obesity drug in MASH. BioPharma Dive, 1 November 2024.
6. Comparing Rezdiffra with Wegovy and Mounjaro In the context of NAFLD/NASH (MASLD/MASH). Fatty Liver Foundation, Accessed 18 December 2024.