Wegovy (semaglutide, Novo Nordisk) and Zepbound (tirzepatide, Eli Lilly) are the two most prescribed injectable weight-management drugs in the United States. They are not interchangeable. Different active ingredients, different mechanisms of action, different FDA-approved indications, different head-to-head evidence, and different payer coverage patterns mean that which one a patient receives depends on a combination of clinical factors and insurance rules.
This comparison is for access teams, prior authorization coordinators, and prescribers who need to navigate the practical differences between the two products.
Short answer
| Wegovy (semaglutide) | Zepbound (tirzepatide) | |
|---|---|---|
| Drug class | GLP-1 receptor agonist | Dual GIP/GLP-1 receptor agonist |
| FDA indications | Chronic weight management, CV risk reduction (CVD + overweight/obesity), noncirrhotic MASH | Chronic weight management, moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity |
| Max maintenance dose (injection) | 2.4 mg weekly (standard), 7.2 mg weekly (Wegovy HD) | 15 mg weekly |
| Formulations | Subcutaneous injection, oral tablet (25 mg) | Subcutaneous injection (single-dose vials, KwikPen) |
| SURMOUNT-5 weight loss (72 wk) | 13.7% average (33.1 lb) | 20.2% average (50.3 lb) |
| List price (approx.) | ~$1,350/month (injection) | ~$1,086/month |
| Commercial copay (with savings card) | As low as $25/month | As low as $25/month |
| Medicare Part D (weight loss alone) | Not covered; CV/MASH indications covered via standard Part D | Not covered; OSA indication may be covered |
| Medicare GLP-1 Bridge eligible | Yes (July 2026–Dec 2027) | Yes (KwikPen only, July 2026–Dec 2027) |
| PA required | Yes (where covered) | Yes (where covered) |
Mechanism of action
Wegovy contains semaglutide, a GLP-1 receptor agonist. It activates the GLP-1 receptor to reduce appetite, slow gastric emptying, and enhance insulin response.
Zepbound contains tirzepatide, a dual GIP and GLP-1 receptor agonist. It activates both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor. The dual mechanism is believed to contribute to greater weight loss compared with GLP-1 monotherapy.
FDA-approved indications
Wegovy indications
- Chronic weight management in adults with BMI ≥30, or ≥27 with at least one weight-related comorbidity (STEP program, approved June 2021). Also approved for pediatric patients aged 12+ with obesity.
- CV risk reduction in adults with established CVD and overweight/obesity without diabetes (SELECT trial, approved March 2024). Wegovy is the only weight-management drug with a specific MACE reduction indication.
- Noncirrhotic MASH with F2–F3 fibrosis in adults (accelerated approval).
- Wegovy HD 7.2 mg for weight management (approved March 2026 under the FDA Commissioner's National Priority Voucher program).
- Wegovy oral tablet 25 mg for weight management (approved December 2025).
Zepbound indications
- Chronic weight management in adults with BMI ≥30, or ≥27 with at least one weight-related comorbidity (SURMOUNT-1 and SURMOUNT-2, approved November 2023).
- Moderate-to-severe obstructive sleep apnea in adults with obesity (SURMOUNT-OSA, approved December 2024 by FDA). Zepbound is the first and only FDA-approved prescription medication for OSA.
The indication differences matter for coverage. Wegovy's cardiovascular indication opens Medicare Part D coverage for patients with established CVD. Zepbound's sleep apnea indication can trigger coverage even when a plan excludes weight-loss medications.
Head-to-head evidence: SURMOUNT-5
The SURMOUNT-5 trial (NCT05822830) is the first head-to-head Phase IIIb study comparing tirzepatide with semaglutide for weight management. Results were published in the New England Journal of Medicine in May 2025.
| Endpoint (72 weeks) | Zepbound (tirzepatide) | Wegovy (semaglutide) |
|---|---|---|
| Average weight loss | 20.2% (50.3 lb / 22.8 kg) | 13.7% (33.1 lb / 15.0 kg) |
| ≥15% weight loss | 64.6% of participants | 40.1% of participants |
| ≥25% weight loss | ~32% of participants | ~16% of participants |
| Waist circumference reduction | 7.2 in (18.4 cm) | 5.1 in (13.0 cm) |
Tirzepatide met the primary endpoint and all five key secondary endpoints, demonstrating superiority over semaglutide for weight reduction. However, the trial was funded by Eli Lilly. The 7.2 mg Wegovy HD dose approved in March 2026 showed roughly 19% weight loss in clinical studies, narrowing but not eliminating the gap.
Dosing and formulations
Wegovy injection
- Titration: 0.25 mg → 0.5 mg → 1 mg → 1.7 mg → 2.4 mg weekly, increasing every 4 weeks
- Wegovy HD: 7.2 mg weekly (approved March 2026)
- Administered once weekly, subcutaneous
Wegovy oral tablet
- Doses: 1.5 mg, 4 mg, 9 mg, 25 mg daily
- Approved December 2025; first oral GLP-1 for weight management
Zepbound injection
- Titration: 2.5 mg → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg weekly, increasing every 4 weeks
- Available as single-dose vials and multi-dose KwikPen (approved February 2026)
- Administered once weekly, subcutaneous
Both drugs require gradual dose titration to manage gastrointestinal side effects (nausea, vomiting, diarrhea, constipation). Both carry an FDA boxed warning for risk of thyroid C-cell tumors based on rodent data.
Coverage comparison by payer
Commercial insurance
| Factor | Wegovy | Zepbound |
|---|---|---|
| Formulary inclusion | Widely covered; preferred GLP-1 on CVS Caremark standard formulary since July 2025 | Removed from CVS Caremark standard commercial formulary July 2025; available via formulary exception |
| Typical tier | Specialty (Tier 3–4) | Specialty (Tier 3–4) or excluded |
| PA criteria | BMI threshold, lifestyle documentation, step therapy, diagnosis-specific criteria | BMI threshold, lifestyle documentation, step therapy, diagnosis-specific criteria |
| Approximate commercial coverage rate | ~45–55% of plans | ~43–45% of plans |
CVS Caremark removed Zepbound from its standard commercial formulary effective July 1, 2025, naming Wegovy the preferred GLP-1. Patients on CVS Caremark plans can request a formulary exception with clinical justification (failed Wegovy, contraindication to semaglutide, or documented superior tirzepatide response). Other PBMs may follow similar moves at renewal.
Approximately 12 million commercially insured people lost coverage for Wegovy and 12 million lost coverage for Zepbound between 2025 and 2026, as many employers and insurers tightened GLP-1 formulary rules, moved GLP-1s to higher tiers, or added weight-loss exclusions.
Medicare Part D
| Factor | Wegovy | Zepbound |
|---|---|---|
| Covered for CV indication | Yes (CVD + overweight/obesity) | Not applicable |
| Covered for MASH | Plan-dependent (accelerated approval) | Not applicable |
| Covered for OSA | Not applicable | Plan-dependent |
| Covered for weight loss alone | No | No |
| 2026 out-of-pocket cap | $2,100/year (IRA) | $2,100/year (IRA) |
| IRA negotiated price | Not yet (semaglutide selected for 2027 round) | Not yet (tirzepatide not yet selected) |
Medicare GLP-1 Bridge (July 2026–December 2027)
On May 7, 2026, CMS announced the Medicare GLP-1 Bridge, a temporary nationwide program running July 1, 2026 through December 31, 2027.
| Factor | Wegovy | Zepbound |
|---|---|---|
| Eligible product | Yes (injection and tablets, all doses) | Yes (KwikPen only) |
| Monthly copay | $50 | $50 |
| Eligibility | BMI ≥30 or BMI ≥27 with qualifying conditions (HF, CKD, prediabetes, prior MI, stroke, symptomatic PAD) | Same criteria |
The Bridge represents the first time Medicare beneficiaries can access weight-management GLP-1s. Prior to this, Medicare Part D explicitly excluded coverage of drugs used solely for weight loss.
Medicaid
Medicaid coverage for both products varies significantly by state. Key patterns:
- California: Removed Zepbound for chronic weight management effective January 2026; sleep apnea requests may still be reviewed. Wegovy restricted to CV and MASH indications.
- Pennsylvania: Zepbound no longer covered for weight-loss-only use; OSA coverage possible with PA criteria met.
- Michigan: Zepbound limited to very high BMI cases for weight loss and OSA; must show prior treatment failures.
- Kentucky: Zepbound coverage centers on sleep apnea with sleep study proof and BMI documentation; generally not covered for weight loss alone.
Most states cover Wegovy and Zepbound more readily when prescribed for non-weight-loss FDA indications (CV risk reduction for Wegovy, OSA for Zepbound).
Cost comparison
| Wegovy | Zepbound | |
|---|---|---|
| List price (injection) | ~$1,350/month | ~$1,086/month |
| Savings card (commercial) | As low as $25/month | As low as $25/month |
| Self-pay (manufacturer pharmacy) | $199–$349/month injection (NovoCare); $149–$299/month tablet | $299–$449/month vials; $299–$699/month KwikPen (Lilly Direct) |
| Patient assistance (uninsured) | Free (≤200% FPL) | Free (≤200% FPL) |
Zepbound has a lower list price but higher self-pay costs at higher doses. Wegovy's oral tablet at $149/month for the starting dose is the lowest-cost FDA-approved GLP-1 option for needle-averse patients.
What changed in 2026
- Wegovy HD 7.2 mg: FDA approved March 19, 2026, under the National Priority Voucher program. Clinical studies showed roughly 19% weight loss, narrowing the efficacy gap with Zepbound.
- Wegovy oral tablet: Launched January 2026 following December 2025 FDA approval. First oral GLP-1 for weight management.
- Zepbound KwikPen: Approved February 2026 as a multi-dose pen option.
- CVS Caremark formulary: Zepbound removed from standard commercial formulary July 2025; Wegovy named preferred GLP-1. This remains in effect through 2026 plan year.
- Medicare GLP-1 Bridge: Announced May 7, 2026; launches July 1, 2026. Both Wegovy (all formulations) and Zepbound KwikPen are eligible at $50/month copay.
- Medicaid tightening: Multiple states restricted GLP-1 coverage for weight-loss-only use effective January 2026, including California, Pennsylvania, and others.
- FDA compounding proposal: On April 30, 2026, FDA proposed excluding semaglutide, tirzepatide, and liraglutide from the 503B Bulk Drug Substances List, restricting compounding access.
- IRA price negotiation: Semaglutide was selected for Medicare price negotiation in the second round; negotiated prices would take effect in 2027.
What to monitor
- IRA price negotiations: Semaglutide negotiated prices for 2027 could significantly reduce Part D costs for Wegovy. Tirzepatide may be selected in a future cycle.
- Medicare GLP-1 Bridge rollout: Monitor CMS guidance on the July 2026 launch, eligible populations, and participating Part D plans. The Bridge is currently scheduled through December 2027.
- Commercial coverage contraction: Ongoing employer and PBM formulary changes during open enrollment.
- CVS Caremark and PBM formulary shifts: If other PBMs follow Caremark's move to prefer Wegovy, Zepbound access could narrow further on commercial plans.
- Zepbound CV outcomes trial: Tirzepatide cardiovascular outcomes data are in development. A positive result could open the same Medicare coverage pathway Wegovy now enjoys.
- Wegovy HD real-world data: The 7.2 mg dose launched April 2026; monitor for real-world persistence and tolerability data.
- MASH confirmatory data: Wegovy's MASH indication is under accelerated approval; monitor for confirmatory trial results.
Sources
- FDA, Wegovy prescribing information: https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s033lbl.pdf
- FDA, Wegovy HD 7.2 mg approval: https://www.fda.gov/news-events/press-announcements/fda-approves-fourth-product-under-national-priority-voucher-program-higher-dose-semaglutide
- FDA, Zepbound OSA approval: https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea
- Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med 2025;393:26-36. DOI: 10.1056/NEJMoa2416394
- Drugs.com, Wegovy FDA approval history: https://www.drugs.com/history/wegovy.html
- Drugs.com, Zepbound FDA approval history: https://www.drugs.com/history/zepbound.html
- Novo Nordisk / PR Newswire, Medicare GLP-1 Bridge announcement (May 7, 2026): https://www.prnewswire.com/news-releases/wegovy-access-expanded-for-medicare-beneficiaries-living-with-obesity-through-the-medicare-glp-1-bridge-starting-july-1-2026-302764949.html
- Eli Lilly and Company, Lilly and U.S. government agree to expand access to obesity medicines: https://lilly.gcs-web.com/news-releases/news-release-details/lilly-and-us-government-agree-expand-access-obesity-medicines
- UnitedHealthcare, Weight Loss/Appetite Suppression Medication Coverage PA criteria (2026): https://www.uhcprovider.com/content/dam/provider/docs/public/prior-auth/drugs-pharmacy/commercial/r-z/PA-Notification-Weight-Loss.pdf
- Medi-Cal Rx, Changes to GLP-1 Drug Coverage effective January 1, 2026: https://medi-calrx.dhcs.ca.gov/cms/medicalrx/static-assets/documents/member/GLP1_Changes.pdf
- AARP, First Medicare-Negotiated Drug Prices Debut in 2026: https://www.aarp.org/medicare/first-medicare-negotiated-drug-prices-debut/
- PMC, Comparative effectiveness of tirzepatide and semaglutide for obesity management: https://pmc.ncbi.nlm.nih.gov/articles/PMC12924827/
