Wegovy vs. Rezdiffra for MASH: ESSENCE vs. MAESTRO-NASH Compared
If you have MASH (the liver disease formerly called NASH) with moderate to advanced scarring, two drugs are FDA-approved for you as of October 2026: Wegovy, a weekly GLP-1 injection, and Rezdiffra, a daily pill that targets the liver directly. Neither is proven to beat the other, because they have never been tested head to head. The better fit usually depends on your weight, your diabetes and heart risk, and whether you are already on a GLP-1.
Key takeaways
- Both drugs carry accelerated FDA approval for adults with noncirrhotic MASH and F2 to F3 fibrosis, based on liver biopsy results rather than long-term outcomes.
- In its own trial, Wegovy resolved steatohepatitis in about 63% of patients versus 34% on placebo at 72 weeks. Rezdiffra resolved it in 26% to 30% versus about 10% on placebo at 52 weeks. These are separate trials, so the numbers are not a direct contest.
- Wegovy also produces substantial weight loss and has proven heart benefits. Rezdiffra acts directly on the liver, so it does not depend on weight loss to work.
- 2026 European guidance suggests semaglutide for people with obesity, diabetes, or high cardiovascular risk, and resmetirom for people without obesity or who cannot use a GLP-1.
- Neither drug is approved for MASH cirrhosis, and combining them is not recommended as a first step.
What each drug is and how it works
Wegovy (semaglutide 2.4 mg) is a once-weekly GLP-1 receptor agonist injection best known for weight loss. The FDA granted it accelerated approval for MASH on August 15, 2025, for adults with noncirrhotic MASH and moderate to advanced fibrosis, used alongside diet and exercise, according to AJMC. In ESSENCE, people on it lost about 10% of their body weight, which likely contributes to its liver effects.
Rezdiffra (resmetirom) is a once-daily oral thyroid hormone receptor-beta agonist from Madrigal Pharmaceuticals. It acts on liver cells to increase fat burning. It received accelerated approval in March 2024 and was the first drug ever approved for this disease, per BioPharma Dive. Its current FDA label doses it by body weight: 80 mg daily under 100 kg and 100 mg daily at 100 kg or more.
The European Commission has also approved Rezdiffra for MASH with moderate to advanced fibrosis, according to Pharma Focus Europe.
ESSENCE vs. MAESTRO-NASH: the trial results side by side
Both approvals rest on liver biopsies taken before and after treatment. Each trial measured two things: whether active inflammation (steatohepatitis) resolved without scarring getting worse, and whether scarring improved by at least one stage without inflammation getting worse.
| Measure | Wegovy (ESSENCE) | Rezdiffra (MAESTRO-NASH) |
|---|---|---|
| Patients in the reported analysis | 800 (first part of a 1,197-person trial) | 955 randomized |
| Fibrosis stages enrolled | F2 or F3 | Mostly F2 to F3 (60% F3, 33% F2) |
| Biopsy timepoint | 72 weeks | 52 weeks |
| Steatohepatitis resolved, no fibrosis worsening | 62.9% vs. 34.3% placebo | 25.9% (80 mg) and 29.9% (100 mg) vs. 9.7% placebo |
| Fibrosis improved, no steatohepatitis worsening | 36.8% vs. 22.4% placebo | 24.2% (80 mg) and 25.9% (100 mg) vs. 14.2% placebo |
| Both outcomes together | 32.7% vs. 16.1% placebo | About 14% to 16% vs. 4.9% placebo |
| Body weight change | About -10.5% vs. -2.0% placebo | Not a reported trial outcome |
| Dosing | Weekly injection | Daily pill |
Cross-trial comparison: different patients, timepoints, and biopsy readers. Sources: Sanyal et al., NEJM 2025 (abstract); ACG Evidence-Based GI summary of Harrison et al., NEJM 2024.
Why you cannot just compare the percentages
Wegovy's headline numbers look about twice as large, but the trials differ in ways that matter. ESSENCE biopsied patients at 72 weeks; MAESTRO-NASH biopsied at 52 weeks. Placebo response was also very different: about a third of ESSENCE placebo patients saw steatohepatitis resolve, versus about one in ten in MAESTRO-NASH. That gap points to differences in trial populations, biopsy reading, and lifestyle counseling rather than drug effects alone.
The fairer way to read them is the gap over placebo. Wegovy's advantage over placebo for steatohepatitis resolution was about 29 percentage points, and about 14 points for fibrosis improvement, per AJMC. Rezdiffra's was roughly 16 to 20 points for resolution and 10 to 12 points for fibrosis. Wegovy's margins look larger, but only a head-to-head trial could confirm that.
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Side effects and safety
The two drugs bother people in different ways.
- Wegovy: Gastrointestinal effects such as nausea, vomiting, and diarrhea were more common than with placebo in ESSENCE, according to the published abstract. In Wegovy's weight-loss trials, 6.8% of people on 2.4 mg stopped for side effects versus 3.2% on placebo, per the Wegovy prescribing information, which also carries a boxed warning about thyroid C-cell tumors.
- Rezdiffra: Diarrhea and nausea are the main issues. In the label's trial data, diarrhea affected 78 of 298 people on 80 mg (about 26%) and 98 of 296 on 100 mg (about 33%), versus about 18% on placebo. The label also limits some statin doses (for example, rosuvastatin and simvastatin to 20 mg daily) and flags interactions with CYP2C8 inhibitors such as clopidogrel and gemfibrozil.
Cost and coverage
Rezdiffra launched at a list price of $47,400 per year, and Madrigal said it expected insurers to require prior authorization but not a liver biopsy, per BioPharma Dive. Uptake has been strong: Madrigal reported more than 49,000 patients on Rezdiffra as of June 30, 2026, and second-quarter 2026 net sales of $364.3 million, in its Q2 2026 earnings release.
Wegovy has a cash option. As of October 2026, NovoCare lists self-pay pricing of $349 per month for the 0.25 mg through 2.4 mg pens, with a $199 introductory price for the first two fills of the starter doses through December 31, 2026. Novo notes the program can change at any time, and self-pay spending does not count toward your deductible. Insurance coverage for the MASH indication varies by plan.
Who each drug tends to fit
In October 2026, the European liver, diabetes, and obesity societies (EASL, EASD, and EASO) issued joint guidance on choosing between the two, as summarized by Medical Dialogues. In short:
- Semaglutide may suit people with obesity, type 2 diabetes, established cardiovascular disease, or high cardiovascular risk. Wegovy separately holds an FDA indication to reduce major cardiovascular events in adults with heart disease and overweight or obesity, per its label.
- Resmetirom may be prioritized for people without obesity, people already on a GLP-1, or people who cannot tolerate one.
- Combination therapy is not recommended as first-line MASH treatment because the evidence is not there yet.
- Response checks: For resmetirom, the guidance suggests assessments at 3, 6, and 12 months and considering stopping if there is little improvement after about a year. Semaglutide may be continued for its heart and metabolic benefits even if liver improvement is limited.
One more practical point: Rezdiffra's benefits appear to depend on staying on it. In an analysis of people who paused treatment, Madrigal reported that benefits waned and generally recovered after restarting, per its November 2025 release. GLP-1 weight loss is also well known to reverse after stopping, so either choice is likely long-term.
What is still unknown
Both approvals are accelerated, which means the FDA is waiting on outcome data showing fewer cases of cirrhosis, liver failure, transplant, or death. The 2026 European guidance notes that randomized trials have not yet definitively shown either drug reduces those long-term liver outcomes. ESSENCE is planned to run 240 weeks, with liver outcome results expected in 2029, per AJMC. Madrigal has a phase 3 outcomes trial in compensated MASH cirrhosis that, as of its mid-2026 update, was still ongoing, with no readout date given.
Madrigal is also developing an oral GLP-1 of its own, MGL-2086, to pair with Rezdiffra. Dosing in its first phase 1 trial began in June 2026, per the same earnings release. That suggests the field expects combination therapy to matter, but for now it remains unproven.
The verdict
For most people with MASH who also carry excess weight, type 2 diabetes, or heart risk, Wegovy is the stronger starting candidate: its trial margins over placebo were larger, it treats the weight and metabolic drivers of the disease, and it has proven cardiovascular benefit. Rezdiffra is the logical choice if you are not overweight, already take a GLP-1, or cannot tolerate one, and it is a once-daily pill. Remember that these results come from separate trials with different designs, and neither drug has yet shown it prevents cirrhosis or liver failure. Bring your fibrosis stage, your other conditions, and your insurance details to your hepatologist or prescriber.
Check what a GLP-1 would cost you
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Frequently asked questions
Is Wegovy or Rezdiffra better for MASH?
They have never been compared head to head. In separate trials, Wegovy showed larger margins over placebo, but the trials used different timepoints and populations, so the results cannot be directly ranked.
Are Wegovy and Rezdiffra approved for MASH cirrhosis?
No. Both are approved for adults with noncirrhotic MASH and moderate to advanced (F2 to F3) fibrosis. Rezdiffra's label says to avoid use in decompensated cirrhosis.
Can I take Wegovy and Rezdiffra together?
October 2026 European guidance says combining them is not recommended as first-line MASH therapy because the evidence is insufficient. Talk to your prescriber about your situation.
How much does Rezdiffra cost?
Rezdiffra launched at a list price of $47,400 per year. What you pay depends on your insurance, and Madrigal expected insurers to require prior authorization.
Do I need a liver biopsy to get either drug?
Rezdiffra's prescribing information does not require a biopsy before treatment. Current European guidance describes noninvasive tests, such as liver stiffness scans, that can help identify eligible patients.
Sources
- AJMC: FDA approves semaglutide for MASH with fibrosis
- Sanyal et al., Phase 3 Trial of Semaglutide in MASH, NEJM 2025 (Medline abstract)
- ACG Evidence-Based GI: MAESTRO-NASH resmetirom trial summary
- Rezdiffra (resmetirom) FDA prescribing information, revised 07/2026
- Wegovy (semaglutide) prescribing information
- BioPharma Dive: Madrigal sets Rezdiffra price and launch plans
- Pharma Focus Europe: European Commission approval for Rezdiffra
- Madrigal Pharmaceuticals Q2 2026 earnings release (SEC filing)
- Madrigal: two-year compensated MASH cirrhosis data (November 2025)
- Medical Dialogues: EASL-EASD-EASO guidance on resmetirom and semaglutide for MASH
- NovoCare: Wegovy self-pay pricing
Medical disclaimer: This article is general information, not medical advice, and does not replace a licensed clinician who knows your history. Approvals, labels, coverage and prices change; check the linked sources and talk with your prescriber or pharmacist before making decisions about any medication.