Side-by-side
| Zepbound | Wegovy | |
|---|---|---|
| Active drug | Tirzepatide | Semaglutide 2.4 mg |
| Drug class | Dual GIP + GLP-1 agonist | GLP-1 agonist |
| Avg weight loss (head-to-head) | −20.2% (−22.8 kg) | −13.7% (−15.0 kg) |
| Dosing | Once-weekly injection | Once-weekly injection |
| Extra FDA approval | Obstructive sleep apnea (obesity) | Cardiovascular risk reduction |
| Cash self-pay (approx.) | $299/mo (2.5 mg) → $449/mo (7.5 mg and up) | $349/mo for maintenance doses |
The head-to-head trial (SURMOUNT-5)
SURMOUNT-5 (New England Journal of Medicine, 2025) randomized 751 adults with obesity but not diabetes to Zepbound or Wegovy, each titrated to its maximum tolerated dose, for 72 weeks. Average weight change was −20.2% with Zepbound vs −13.7% with Wegovy(about −22.8 kg vs −15.0 kg; waist −18.4 cm vs −13.0 cm; p<0.001). It is the first and only trial to test the two brands directly, which is why it settles the “which loses more weight on average” question that cross-trial comparisons never could.
Two honest caveats. First, doses were titrated to what each person tolerated, so not everyone reached the top dose — this reflects real-world use, but it is not “top dose vs top dose.” Second, “more on average” is a group result; plenty of people do excellently on Wegovy. For the fuller efficacy picture see our GLP-1 weight-loss results and the ingredient hubs for semaglutide and tirzepatide.
Beyond weight: the extra approvals
A tie-breaker many people miss is what else each drug is approved to do:
- Wegovy is FDA-approved to reduce cardiovascular risk (heart attack, stroke, cardiovascular death) in adults with established heart disease and overweight/obesity — the first weight-loss drug to earn that indication (March 2024), based on the SELECT trial. If you have heart disease, that matters. See GLP-1s and heart health.
- Zepbound is FDA-approved for moderate-to-severe obstructive sleep apnea in adults with obesity — see Zepbound for sleep apnea.
Cost and coverage
Both list above $1,000/month, so most people rely on insurance or manufacturer cash programs. As of 2026, Wegovy's cash self-pay is about $349/mo for maintenance doses ($199/mo for the first 2 fills, then $349 introductory), and Zepbound self-pay starts near $299/mo (2.5 mg) and rises to about $449/mo (7.5 mg and up) at maintenance on the refill schedule. Coverage varies widely by plan. Compare current numbers on our cheapest GLP-1 page.
The real annual cost gap
Cash prices are quoted monthly, which hides the number that actually decides this for many people. At maintenance, paying cash:
| Path | Per month | Per year |
|---|---|---|
| Wegovy cash, maintenance | $349 | ~$4,188 |
| Zepbound, refilled within window | $449 | ~$5,388 |
| Zepbound, window missed | $699 | ~$8,388 |
Note the third row. Lilly's discounted maintenance price is conditional on buying each refill within 45 days of the previous one. Miss that window and the same dose costs $250 more per month — roughly $3,000 a year, purely from refill timing. If you are choosing on price, that condition belongs in the comparison alongside the headline figures.
The practical differences you live with
| Zepbound | Wegovy | |
|---|---|---|
| In-use storage | Up to 21 days after first use | Depends on the device — check your pen |
| Device | Single-dose pen or vial | Single-dose pen, or a multi-dose FlexTouch pen |
| If you miss a dose | Take within 4 days, then resume | Take within 5 days, then resume |
| Changing your dose day | Leave at least 72 hours | Leave at least 48 hours |
| Refill timing affects price | Yes — 45-day window on cash pricing | No equivalent window |
Wegovy now exists in more than one device format, so “Wegovy is single-dose” is no longer a safe blanket statement — check the pen you were actually dispensed. Always follow your own product's instructions; these windows are drug-specific.
Which one fits your situation?
| If this is you | Worth raising with your clinician |
|---|---|
| Established cardiovascular disease | Wegovy carries a cardiovascular-risk-reduction indication — a real on-label advantage |
| Moderate-to-severe obstructive sleep apnea | Zepbound is approved for OSA in obesity, which can open coverage where weight-loss drugs are excluded |
| Maximum average weight loss is the priority | Zepbound won the only head-to-head — though group averages are not individual outcomes |
| Your plan covers only one of them | Formulary position usually decides this; an exception is possible if the covered one fails you |
| Paying cash and refilling irregularly | Wegovy pricing is flat; Zepbound's discount depends on refilling on schedule |
| Nausea has been a problem before | Titration pace matters more than the molecule — discuss the escalation plan |
Coverage routes: Wegovy PA · Zepbound PA and the sleep-apnea route · appealing a denial.
Switching between them
People switch often — usually because a plan changed its formulary, or because of side effects or an inadequate response. It is a clinical decision rather than a dose conversion: there is no published table mapping a semaglutide dose onto an equivalent tirzepatide dose, because the drugs have different mechanisms and different dose ladders. A switch normally means restarting titration on the new drug, so expect the early gastrointestinal effects to return for a while.
Confirm coverage for the new drug before stopping the old one. And if the switch is being forced by your plan rather than chosen with your clinician, that is a formulary problem with its own remedy — see formulary exceptions.
Both are prescription medications with real risks (including a boxed thyroid-tumor warning) and aren't right for everyone. This page is educational, dated 2026-07-18, and not medical advice — the choice belongs with a licensed clinician.