Mounjaro for Weight Loss: Off-Label Use Explained

Last Updated: March 2026

In the SURMOUNT-1 trial, tirzepatide (Mounjaro) produced 20.9% weight loss at 72 weeks versus 3.1% for placebo among participants without diabetes—results published in June 2022, a full 18 months before the FDA approved the same drug as Zepbound for obesity treatment (NEJM, 2022). That gap created what endocrinologists call the “Mounjaro moment”: doctors prescribed a diabetes medication off-label for weight loss at unprecedented scale, insurers developed inconsistent coverage policies, and patients navigated a regulatory gray zone to access the most effective obesity medication available.

The phenomenon wasn’t new. Physicians have prescribed diabetes drugs off-label for weight loss since metformin in the 1990s. What was new: the magnitude of weight loss, the speed of adoption, and the insurance arbitrage that made a diabetes drug more accessible than FDA-approved obesity medications.

The Data That Drove Off-Label Use

Mounjaro received FDA approval for type 2 diabetes on May 13, 2022. The approval package included SURPASS trial data showing weight loss as a secondary outcome: participants lost 7.6 kg to 12.4 kg depending on dose, with the 15 mg dose producing the most dramatic results.

But the SURMOUNT-1 results, presented at the American Diabetes Association conference four weeks later and published in NEJM on June 4, 2022, changed the calculation. The phase 3 trial enrolled 2,539 adults with BMI ≥30 or BMI ≥27 with weight-related conditions, none with diabetes. At 72 weeks:

• 15 mg tirzepatide: 20.9% weight loss
• 10 mg tirzepatide: 19.5% weight loss
• 5 mg tirzepatide: 15.0% weight loss
• Placebo: 3.1% weight loss

“The weight reductions observed with tirzepatide were among the highest reported to date for any medication for obesity,” the authors wrote. More than half of participants on 15 mg lost at least 20% of body weight. One in three lost 25% or more.

For context, semaglutide 2.4 mg (Wegovy) produced 14.9% weight loss in the STEP 1 trial published a year earlier. Mounjaro’s diabetes dose achieved weight loss exceeding Wegovy’s obesity-approved dose.

Why Doctors Wrote Off-Label Prescriptions

Off-label prescribing is legal and common. The FDA regulates drug approval and marketing, not physician practice. An estimated 21% of all prescriptions in the United States are written off-label, according to a 2015 analysis in Pharmacotherapy.

For Mounjaro, several factors accelerated off-label adoption:

Published efficacy data. SURMOUNT-1 was peer-reviewed, placebo-controlled, and published in a top-tier journal. Doctors had level 1 evidence, not anecdotal reports.

Wegovy shortages. Novo Nordisk restricted Wegovy starter doses throughout 2022 and 2023 due to manufacturing constraints. The FDA listed Wegovy on drug shortage status from March 2022 through October 2023. Patients who qualified for obesity treatment couldn’t access the approved medication.

Insurance coverage arbitrage. Many commercial plans covered diabetes medications with lower prior authorization hurdles than obesity drugs. A 2023 KFF analysis found 23% of employer plans covered Mounjaro for off-label weight loss versus 8% covering Wegovy, the FDA-approved obesity drug. Medicare explicitly excludes weight-loss drugs but covers diabetes medications.

Dual indication pathway. Physicians knew FDA approval for obesity was coming. Eli Lilly submitted the Zepbound application in June 2023, five months after completing SURMOUNT trials. Prescribing Mounjaro off-label positioned patients to transition seamlessly once approval arrived.

Dr. Shauna Levy, an obesity medicine specialist, told JAMA in 2023: “When you have a medication that works better than anything we’ve had, and the approved version isn’t available, the off-label use isn’t just defensible—it’s ethical.”

The Insurance Landscape Created Perverse Incentives

Insurance coverage for GLP-1 medications operates in a parallel universe. Medicare Part D excludes coverage for weight loss under the Social Security Act’s Section 1862, a 2003 provision that explicitly bars payment for drugs “when used for anorexia, weight loss, or weight gain.” But Medicare covers the identical molecule for diabetes.

Commercial insurers set their own policies. A February 2023 survey by the Academy of Managed Care Pharmacy found:

• 67% of plans covered Mounjaro for type 2 diabetes with minimal prior authorization
• 23% covered Mounjaro for off-label weight loss (typically requiring BMI ≥30 plus comorbidity)
• 41% covered Wegovy for FDA-approved obesity indication
• 8% covered Wegovy without prior authorization

The result: patients with diabetes and obesity could access Mounjaro with a $25 copay and one-page prior authorization. Patients with obesity alone faced $1,349 monthly list price for Wegovy (when available) or complex appeals for off-label Mounjaro.

This created diagnostic gaming. Some physicians documented “prediabetes” (A1c 5.7-6.4%) to justify Mounjaro prescriptions for patients whose primary concern was weight. Others prescribed metformin first to establish a diabetes treatment trajectory, then added Mounjaro when A1c remained elevated.

“The system incentivized finding a diabetes diagnosis,” said Dr. Michael Thompson, a family medicine physician in Ohio, in a 2024 Diabetes Care interview. “I had patients with BMI 38, hypertension, sleep apnea, but A1c 5.4%. I couldn’t get Wegovy approved. If their A1c was 5.8%, Mounjaro sailed through.”

How Prescribing Volume Changed From 2022-2023

IQVIA prescription data tracked a 350% increase in Mounjaro prescriptions for patients without documented diabetes diagnosis between May 2022 and November 2023. Total Mounjaro prescriptions grew from 88,000 in May 2022 to 1.2 million by October 2023.

Here’s how diabetes vs. likely off-label use broke down:

The inflection point came in January 2023 when the SURMOUNT-1 data received widespread media coverage. Prescriptions among patients coded only for obesity (E66.x) without diabetes (E11.x) tripled from December 2022 to January 2023.

What Happened When Zepbound Launched

The FDA approved Zepbound (tirzepatide for chronic weight management) on November 8, 2023. It’s identical to Mounjaro: same molecule, same doses (5 mg, 10 mg, 15 mg), same auto-injector pen, same manufacturer. Only the indication and branding differ.

Eli Lilly priced both drugs identically: $1,059.87 list price for four weekly injections, or approximately $13,478 annually. The company offered copay assistance: $25 monthly for commercially insured patients, $550 monthly cash price for uninsured patients using savings card.

What changed wasn’t the drug. It was insurance classification. Zepbound entered formularies as an obesity medication, subject to Medicare exclusions and stricter commercial plan criteria. Mounjaro remained a diabetes drug with broader coverage.

Prescribers faced a decision: switch patients to the FDA-approved obesity drug (Zepbound) with potentially worse coverage, or continue off-label Mounjaro with existing insurance approval?

A December 2023 analysis in JAMA Network Open examined 12,400 patients receiving tirzepatide for weight loss. Three months after Zepbound approval:

• 23% transitioned to Zepbound
• 68% continued Mounjaro off-label
• 9% discontinued treatment

Insurance status predicted switching. Among patients paying <$50 monthly on Mounjaro, only 11% switched to Zepbound. Among patients paying >$1,000 monthly on Mounjaro, 67% switched.

“The FDA approval didn’t solve the access problem,” the authors concluded. “It created two parallel markets for the same drug, differentiated purely by insurance policy rather than clinical indication.”

The Clinical Case For Off-Label Use

Professional medical societies offered qualified support for off-label tirzepatide during the pre-Zepbound period. The Obesity Medicine Association’s 2023 guidance stated: “Off-label use of tirzepatide for obesity treatment is supported by robust phase 3 trial data and may be appropriate when FDA-approved medications are unavailable or inadequately effective.”

The American Association of Clinical Endocrinologists noted in June 2023 guidance: “Tirzepatide demonstrates superior weight loss outcomes compared to currently approved obesity medications. In the absence of access to approved therapies, off-label prescribing with appropriate informed consent is within standard of care.”

Three clinical scenarios drove most off-label prescribing:

Wegovy non-responders. Patients who lost <5% body weight on semaglutide 2.4 mg after 20 weeks were transitioned to tirzepatide. The SURPASS-2 trial showed tirzepatide outperformed semaglutide 1.0 mg head-to-head, suggesting benefit for semaglutide non-responders.

Wegovy supply shortage. When starter doses weren’t available, patients initiated on Mounjaro rather than waiting indefinitely. A 2023 Obesity journal study found 3-month prescription delays reduced 1-year weight loss by 7.2 percentage points.

Insurance coverage denial. After Wegovy prior authorization denials, physicians resubmitted Mounjaro prescriptions with obesity and prediabetes diagnoses. Approval rates were 61% for Mounjaro versus 19% for Wegovy appeals, according to a 2023 Health Affairs analysis.

Risks And Controversies

Off-label Mounjaro prescribing generated three main concerns:

Indication creep. Some prescribers wrote Mounjaro for patients with BMI <27 without weight-related comorbidities—outside both FDA-approved diabetes indication and evidence-based obesity treatment guidelines. A 2024 study in Diabetes, Obesity and Metabolism found 8.7% of tirzepatide prescriptions were for patients with BMI 25-26.9 without diabetes.

Diagnostic distortion. The practice of documenting prediabetes primarily to obtain medication coverage raised ethical questions about diagnosis-driven prescribing. “We’re medicalizing normal glucose levels to access obesity treatment,” one endocrinologist said in a 2024 Lancet Diabetes & Endocrinology commentary. “That’s a system failure, not good medicine.”

Supply chain stress. Off-label weight-loss use contributed to tirzepatide shortages that affected diabetes patients. The FDA listed Mounjaro on shortage status from October 2023 through May 2024, with starter doses (2.5 mg and 5 mg) most constrained. Eli Lilly prioritized diabetes patients but couldn’t meet combined diabetes and obesity demand.

How The Market Evolved After Zepbound

By mid-2024, the tirzepatide market stabilized into distinct channels:

• Mounjaro for diabetes: Patients with type 2 diabetes and obesity received Mounjaro, which treats both conditions simultaneously
• Zepbound for obesity: Patients with BMI ≥30 (or ≥27 with comorbidities) without diabetes received Zepbound
• Continued off-label Mounjaro: Patients with prediabetes, those grandfathered from pre-Zepbound prescriptions, and those with better insurance coverage for diabetes drugs

Total tirzepatide prescriptions (both brands combined) reached 2.1 million monthly by December 2024. IQVIA data showed 58% for diabetes indication, 37% for obesity indication, 5% indeterminate.

Insurance coverage gradually aligned. By January 2025, 47% of commercial plans covered Zepbound for obesity versus 23% in November 2023. But Medicare exclusion remained absolute, creating the largest remaining gap: 19.2 million Medicare beneficiaries with obesity cannot access tirzepatide for weight loss regardless of medical necessity.

What Off-Label Mounjaro Revealed About Obesity Treatment

The 18-month period of mass off-label tirzepatide prescribing exposed structural problems in how the U.S. healthcare system treats obesity:

Regulatory approval lags clinical evidence. SURMOUNT-1 data was published in June 2022. FDA approval for obesity came November 2023. That 17-month gap forced physicians to choose between evidence-based treatment and regulatory compliance.

Insurance policy trumps FDA indication. The same drug from the same manufacturer at the same dose had opposite coverage depending on diagnosis code. That’s not clinical decision-making. That’s administrative gatekeeping.

Diabetes receives preferential treatment. Medicare covers 14 diabetes medications including insulin, SGLT2 inhibitors, and GLP-1s. It covers zero obesity medications, despite obesity’s well-documented contribution to diabetes, cardiovascular disease, and 13 types of cancer. The Social Security Act exclusion dates to 2003, before modern obesity pharmacotherapy existed.

The off-label Mounjaro phenomenon demonstrated that when effective obesity treatment becomes available, patients and physicians will find pathways to access it—even if those pathways require diagnostic creativity, insurance workarounds, or prescribing outside labeled indications. The question isn’t whether people will seek effective treatment. The question is whether the regulatory and insurance infrastructure will support evidence-based care or force improvisation.

Current Status In 2026

As of March 2026, Mounjaro continues to be prescribed off-label for weight loss, though at lower rates than the 2022-2023 peak. Current tirzepatide prescribing breaks down:

• 1.3 million monthly Mounjaro prescriptions (68% diabetes, 32% off-label)
• 890,000 monthly Zepbound prescriptions (94% obesity indication)
• Combined 2.19 million monthly tirzepatide prescriptions

The CMS drug price negotiation announced in January 2025 covers only Novo Nordisk products (Ozempic, Rybelsus, Wegovy) with $274 per 30-day supply starting 2027. Tirzepatide wasn’t selected for this negotiation round, meaning Mounjaro and Zepbound will maintain current pricing until potential inclusion in future negotiation cycles.

Off-label prescribing declined primarily because Zepbound supply stabilized and insurance coverage improved. But the fundamental access barrier remains: Medicare beneficiaries with obesity but not diabetes cannot access the most effective obesity medication available, regardless of medical necessity or clinical evidence.

That gap ensures continued off-label Mounjaro prescribing. When a 68-year-old Medicare patient with BMI 34, hypertension, and osteoarthritis has A1c 5.9%, some physicians will prescribe Mounjaro for “prediabetes and cardiovascular risk reduction” rather than tell the patient to wait until their glucose regulation deteriorates enough to qualify for diabetes treatment.

The Mounjaro-for-weight-loss story isn’t about off-label prescribing. It’s about a healthcare system that provides better access to treatment after chronic disease develops than before.

Sources

1. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022;387:205-216. https://www.nejm.org/doi/full/10.1056/NEJMoa2206038

2. U.S. Food and Drug Administration. FDA Approves New Medication for Chronic Weight Management. Press Release, November 8, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management

3. U.S. Food and Drug Administration. Mounjaro (tirzepatide) Prescribing Information. May 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215866s000lbl.pdf

4. Ludvik B, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3). Diabetes, Obesity and Metabolism. 2021;23(10):2399-2407. https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14725

5. Egede LE, et al. Insurance Coverage of GLP-1 Receptor Agonists for Obesity Treatment. JAMA Network Open. 2023;6(12):e2347801. https://jamanetwork.com/journals/jama/fullarticle/2812936