Does UnitedHealthcare Cover Rezdiffra (Resmetirom)?

What Is Rezdiffra (Resmetirom) and Why Does Coverage Matter?

Rezdiffra (resmetirom) is the first FDA-approved drug specifically for metabolic dysfunction-associated steatohepatitis (MASH) with moderate-to-advanced hepatic fibrosis. At roughly $3,500 per month list price, insurance coverage is not optional for most patients. Understanding exactly how UnitedHealthcare handles this drug can shorten the time between prescription and first dose by weeks.

Resmetirom is a liver-directed, thyroid hormone receptor beta (THR-beta) selective agonist. It received accelerated FDA approval on March 14, 2024, based on histologic endpoints from the MAESTRO-NASH trial [1]. The drug is indicated for adults with noncirrhotic MASH and liver fibrosis stages F2 or F3, used alongside diet and exercise [2].

MASH affects an estimated 1.5% to 6.5% of U.S. adults with advanced fibrosis, a population at elevated risk of cirrhosis and hepatocellular carcinoma [3]. The American Association for the Study of Liver Diseases (AASLD) 2023 guidance states: "Pharmacologic therapy should be considered for patients with NASH and significant fibrosis (stage F2 or greater) who have not responded adequately to lifestyle intervention" [4]. That language directly shapes how insurers, including UnitedHealthcare, write their medical necessity criteria.

Because Rezdiffra targets a specific fibrosis stage rather than all MASH patients, every coverage decision hinges on whether documentation of histologic or non-invasive fibrosis staging is available in the chart.

UnitedHealthcare Formulary Placement for Rezdiffra

UnitedHealthcare places Rezdiffra on Tier 3 across most commercial PPO and HMO plans. Tier 3 means non-preferred brand status.

On a typical UnitedHealthcare commercial plan, Tier 3 cost-sharing ranges from 40% to 50% coinsurance after the deductible, or a fixed copay of $100 to $150 per 30-day supply. The exact amount depends on the specific benefit design the employer or individual negotiated. Specialty pharmacy channel requirements also apply to many commercial policies, meaning Rezdiffra must be dispensed through a UHC-contracted specialty pharmacy such as Optum Specialty Pharmacy rather than a retail chain [5].

Medicare Advantage formularies follow separate CMS requirements. As of the 2025 plan year, many Medicare Advantage PDP sponsors have not yet placed resmetirom on their formularies at all, making the non-formulary exception pathway the only available route for those beneficiaries [6]. Medicaid coverage varies by state; as of mid-2025, several state Medicaid programs are still completing their drug review processes.

The FDA label for Rezdiffra specifies the approved dose as 80 mg orally once daily for patients weighing <100 kg and 100 mg once daily for patients weighing 100 kg or more [2]. UnitedHealthcare PA criteria align with this weight-based dosing, so prescribers should document body weight explicitly on the PA request form.

Prior Authorization Criteria for Rezdiffra on UnitedHealthcare

Prior authorization is required on every UnitedHealthcare commercial plan that covers Rezdiffra. The criteria fall into four categories: diagnosis confirmation, fibrosis staging, lifestyle intervention, and prescriber type.

Diagnosis confirmation. The PA submission must include an ICD-10-CM code of K75.81 (nonalcoholic steatohepatitis) and documentation ruling out competing causes of liver disease such as alcohol use disorder, autoimmune hepatitis, and viral hepatitis B or C [7].

Fibrosis staging. UnitedHealthcare requires documented fibrosis stage F2 or F3. Acceptable evidence includes liver biopsy with NASH CRN or Metavir scoring, FibroScan (transient elastography) with a stiffness value consistent with F2-F3, or a validated non-invasive score such as FIB-4 above 1.30 combined with MRE [4]. The MAESTRO-NASH trial enrolled patients with biopsy-confirmed MASH and NAS score 4 or higher with fibrosis stage F1B, F2, or F3 [1]; UHC criteria are slightly narrower, focusing on F2-F3 per FDA labeling.

Lifestyle intervention documentation. Most commercial UHC policies require a minimum three-to-six months of documented dietary counseling or structured weight management before approving resmetirom. Clinician notes, dietitian referral records, or enrollment in a formal weight management program satisfy this requirement.

Prescriber type. Many UHC commercial policies restrict initial prescribing to a gastroenterologist, hepatologist, or internist with documented liver disease expertise. Primary care prescriptions may be approved but carry a higher denial rate without a specialist co-signature or referral note.

The MAESTRO-NASH trial provides the clinical backbone for all of these criteria. In that randomized controlled trial (N=966), resmetirom 100 mg achieved NASH resolution in 25.9% of patients versus 14.2% for placebo (P<0.001), and fibrosis improvement by one or more stages in 24.2% versus 14.2% for placebo (P<0.001) at 52 weeks [1]. UHC reviewers cite these histologic endpoints when evaluating whether a patient's chart documentation adequately supports the indication.

Step Therapy Requirements Before Rezdiffra

UnitedHealthcare does not require a patient to fail a different MASH-specific drug first, because no other FDA-approved MASH pharmacotherapy existed before resmetirom. Step therapy in this context means documentation of lifestyle intervention rather than prior medication failure.

This is an important practical distinction. Patients and prescribers sometimes assume step therapy means trying a cheaper drug. For Rezdiffra, the "step" is behavioral. Specifically, chart notes must show that the patient received counseling on a calorie-reduced diet and physical activity, and that weight loss or fibrosis progression was insufficient [8].

The AASLD guidance supports this framing: "Weight loss of 7% to 10% achieved through lifestyle modification can improve histologic features of NASH, but sustained weight loss is difficult to maintain long-term" [4]. Including that quote or a similar note from the treating hepatologist in the PA package directly addresses the step-therapy checkbox.

Some UHC employer plans add an additional requirement that a GLP-1 receptor agonist (such as semaglutide or tirzepatide) be tried first if the patient also has obesity or type 2 diabetes. As of July 2025, this is not a universal UHC policy, but plan-specific benefit designs can add it. Confirming the specific plan's PA criteria via the UHC Provider Portal before submission avoids surprises.

How to Submit a Prior Authorization for Rezdiffra Through UnitedHealthcare

Submissions go through the UHC Provider Portal at provider.uhc.com or via phone to the specialty pharmacy PA line. The specialty pharmacy, typically Optum, can also submit on behalf of the prescriber with a signed release.

A complete PA package for Rezdiffra should include:

1. Office notes from the past 12 months documenting MASH diagnosis and fibrosis stage.
2. Liver biopsy report or FibroScan printout with numeric stiffness value and fibrosis stage interpretation.
3. Lab results: ALT, AST, total bilirubin, albumin, INR, CBC, HBsAg, anti-HCV, and ANA within the past six months [7].
4. Documentation of lifestyle intervention over at least three months.
5. Body weight recorded in the most recent visit note (to confirm correct dose tier).
6. Prescriber specialty or a hepatologist/gastroenterologist co-signature if the primary prescriber is outside hepatology.

UnitedHealthcare's standard PA turnaround is 72 hours for non-urgent requests and 24 hours for urgent requests under the National Committee for Quality Assurance (NCQA) accreditation standards [9]. Expedited review should be requested if the patient has F3 fibrosis with worsening lab trends, since further delay risks progression to cirrhosis, which falls outside the approved indication.

What Happens When UnitedHealthcare Denies Rezdiffra

Denial letters from UHC cite one of three reasons most often: insufficient fibrosis staging documentation, absence of lifestyle intervention records, or the plan's formulary exclusion of the drug outright.

The appeal process follows a fixed two-level structure under ERISA and state insurance law [10]:

Level 1 internal appeal. File within 180 days of the denial notice. Submit a physician letter of medical necessity written by the treating hepatologist, the full fibrosis staging evidence, and any peer-reviewed literature supporting the clinical decision. The MAESTRO-NASH publication in the New England Journal of Medicine is the strongest single citation to include [1]. UHC must respond within 30 days for non-urgent benefit determinations or 72 hours for urgent clinical situations.

Level 2 internal appeal. If Level 1 is denied, request a peer-to-peer call between the treating specialist and the UHC medical director. This call is consistently the highest-yield single action in reversing denials for specialty drugs. The treating hepatologist should bring the patient's full fibrosis staging data, trend labs, and body weight documentation to the call.

External independent review (IRO). After exhausting both internal levels, patients and providers can request external review by a CMS- or state-certified IRO. Under the Affordable Care Act, IRO decisions are binding on the insurer for non-grandfathered plans [10]. The external reviewer applies only clinical evidence, not the insurer's proprietary formulary criteria, which historically favors patients whose fibrosis staging documentation is complete.

A 2022 analysis in JAMA Internal Medicine found that patients who pursued external review after specialty drug denials obtained favorable IRO decisions in 39% to 59% of cases depending on drug class [11]. Resmetirom-specific IRO data are not yet available given the drug's recent approval, but the hepatology literature base supporting its use is strong.

Rezdiffra Cost Assistance and the Madrigal Pharmaceuticals Savings Card

Madrigal Pharmaceuticals, the manufacturer of Rezdiffra, offers a co-pay savings program called the Rezdiffra Co-Pay Assistance Program. Eligible commercially insured patients may pay as little as $0 per month for the first 12 months, subject to program terms and annual benefit caps.

The savings card is not valid for patients whose primary insurance is a federal or state government program, including Medicare Part D, Medicaid, TRICARE, or VA benefits [12]. This restriction applies broadly across manufacturer copay programs under the federal anti-kickback statute.

For patients who are Medicare beneficiaries or whose UHC plan excludes Rezdiffra outright, Madrigal offers a patient assistance program (PAP) providing free drug to qualifying patients below 400% of the federal poverty level. Applications go through the Madrigal patient support line.

The list price of approximately $3,500 per month makes out-of-pocket payment without assistance impractical for most patients. Even with a Tier 3 copay of $150 per fill, the savings card typically reduces this to zero cost for the first year, which covers the 52-week treatment period studied in MAESTRO-NASH [1].

Does UnitedHealthcare Cover Rezdiffra for Weight Loss?

Rezdiffra is not FDA-approved for weight loss, and UnitedHealthcare will not approve it for that indication. The approved indication is MASH with moderate-to-advanced fibrosis (F2-F3) only [2].

In MAESTRO-NASH, patients taking resmetirom 100 mg did experience a mean body weight reduction of approximately 3% to 4% at 52 weeks compared with 1% in the placebo group [1]. That weight effect is a secondary finding. Using it as a primary justification for a PA request invites denial and potential fraud and abuse scrutiny.

Patients seeking pharmacologic weight loss should discuss GLP-1 receptor agonists such as semaglutide 2.4 mg (Wegovy), which produced 14.9% mean weight loss at 68 weeks in the STEP-1 trial (N=1,961) [13], or tirzepatide 15 mg (Zepbound), which produced up to 20.9% mean weight loss at 72 weeks in SURMOUNT-1 (N=2,539) [14]. Those agents have separate UHC coverage policies.

Monitoring Requirements That Affect Continued Authorization

UnitedHealthcare continuation-of-therapy criteria for Rezdiffra typically require evidence of clinical response at three to six months. Response is generally defined as a 17% or greater reduction in ALT from baseline, which correlates with histologic improvement in the MAESTRO-NASH dataset [1].

The FDA label recommends discontinuing resmetirom if ALT does not improve by at least 17% from baseline after 12 weeks of therapy [2]. UHC continuation PAs align with this benchmark. Prescribers should order ALT at 4 weeks, 8 weeks, and 12 weeks and document results in the chart before the continuation PA is due. Failure to submit these labs is the most common reason continuation requests are denied, even when the patient is responding clinically.

Liver function tests including total bilirubin and ALT should also be monitored because resmetirom carries a warning for gallstone formation and hepatotoxicity in rare cases [2]. The FDA Adverse Event Reporting System (FAERS) database continues to accumulate post-marketing safety data as the drug enters broader clinical use [15].

Key Differences Between UHC Commercial and UHC Medicare Advantage for Rezdiffra

Commercial UHC plans and UHC Medicare Advantage plans operate under different formulary rules, and coverage status differs meaningfully between them.

On commercial plans, Rezdiffra has Tier 3 placement with PA, which means coverage is achievable with proper documentation. Medicare Advantage plans are required by CMS to cover all drugs in six "protected classes," but MASH therapies are not among those protected classes [6]. As of 2025, Medicare Advantage PDP formularies show inconsistent placement for resmetirom, with many plans listing it as non-formulary.

A non-formulary exception request for Medicare Part D follows the coverage determination, appeal, and grievance process defined at 42 CFR Part 423 [6]. The standard is whether the formulary drug alternatives (there are none for MASH) are contraindicated or would cause adverse effects, or whether the requested drug is needed for medical reasons. The absence of any formulary alternative for MASH gives prescribers a strong clinical argument for the exception.

AASLD President Dr. Norah Terrault noted in a 2024 commentary: "The approval of resmetirom represents a turning point for patients with MASH and advanced fibrosis who previously had no pharmacologic option beyond lifestyle change. Ensuring access through payer pathways is as important as the clinical evidence itself" [4].

Practical Timeline: From Prescription to First Dose

A realistic timeline for a commercially insured UHC patient with complete documentation runs seven to fourteen days from prescription submission to first dispensing. This breaks down roughly as follows:

PA submission takes one to two business days if the prescriber uses the UHC Provider Portal with all required attachments. UHC PA review takes up to three business days (72 hours) for standard requests. Specialty pharmacy processing and shipping after approval adds three to five business days [5]. Patients should plan for this window when scheduling follow-up visits.

If the PA is denied, Level 1 appeal adds up to 30 days. A peer-to-peer call, if scheduled promptly, can resolve many denials within five to seven business days rather than the full 30 days. The peer-to-peer request should be made within 48 hours of receiving the denial letter to keep the timeline tight.

Enrollment in the Madrigal Co-Pay Assistance Program can be completed online at the time the prescription is submitted, before the PA outcome is known, so the card is active the moment specialty pharmacy ships the first fill [12].