Wegovy vs Zepbound: 20.2% Against 13.7%, and Why That Is Not the Whole Answer

Last reviewed 27 August 2026 · Educational, not medical advice · No sponsorships, no affiliate links

SURMOUNT-5 is the trial that matters

Nearly every other comparison of these two products lines up numbers from separate studies with different populations and different conventions. SURMOUNT-5 does not have that problem. It enrolled 751 adults with obesity or overweight with a weight-related condition, randomised them one-to-one, and ran both drugs to maximum tolerated dose - tirzepatide at 10 or 15 mg, semaglutide at 1.7 or 2.4 mg - for 72 weeks.

Tirzepatide won the primary endpoint by 6.5 percentage points of body weight, which is 47% more relative weight loss. It also won on waist circumference, systolic and diastolic blood pressure, HbA1c, fasting insulin, triglycerides, and HDL cholesterol. There was no endpoint on which semaglutide came out ahead.

Two things are worth holding on to. First, this is the treatment-regimen result - everyone randomised, whether or not they stayed on the drug - so it is the number closest to what a clinic sees, not the flattering adherent-completer figure that usually reaches press releases. Second, it tested semaglutide at 2.4 mg, which was the ceiling at the time. Wegovy HD at 7.2 mg was approved in March 2026 and reached 20.7% in its own trial, STEP UP. Nobody has run 7.2 mg against tirzepatide, so the current ceiling-to-ceiling question is genuinely open.

The tolerability result that runs against intuition

A drug that hits two receptors ought to be harder to tolerate than one that hits one. SURMOUNT-5 found the reverse: gastrointestinal adverse events led 2.7% of tirzepatide patients to stop the drug against 5.6% on semaglutide, roughly a two-fold difference in the unexpected direction.

This matters more than it first appears, because it removes the trade-off most people assume they are making. You are not buying extra weight loss with extra nausea. Both drugs produce nausea, constipation, diarrhoea and vomiting, mostly mild to moderate, mostly clustered in the weeks after a dose increase. The strongest lever on whether you tolerate either is how fast you climbed the ladder, not which ladder you picked.

Which drug your comorbidity picks for you

The weight numbers are the least interesting part of this comparison for anyone who has a second diagnosis. The two products have collected non-overlapping indications, and each was earned in a trial the other company has not run.

Wegovy reduced major adverse cardiovascular events by 20% against placebo in SELECT, across 17,604 adults with cardiovascular disease and obesity but no diabetes. It received accelerated approval in August 2025 for MASH with moderate-to-advanced fibrosis - the first GLP-1 drug approved for a liver indication.

Zepbound was approved in December 2024 for moderate-to-severe obstructive sleep apnea in adults with obesity, the first drug approval for that condition in any class. Tirzepatide has no placebo-controlled cardiovascular outcome trial; SURPASS-CVOT tested it against dulaglutide and found non-inferiority.

What each one costs per point of weight lost

Zepbound is the more expensive prescription and the better value, because the denominator moves faster than the numerator. Priced at US manufacturer self-pay rates in August 2026, replicating the SURMOUNT-5 course costs about $7,882 for Zepbound and $6,282 for Wegovy over 72 weeks. Divide by what each achieved and you get $390 per percentage point against $459.

The workings, so you can redo them: Zepbound $299 (2.5 mg) + $399 (5 mg) + 16 fills at $449 = $7,882; Wegovy 18 fills at $349 = $6,282. One trap worth knowing about on the Lilly side: the 12.5 mg and 15 mg vials revert to $849 and $1,049 if you do not refill within 45 days, so a lapse is expensive in a way the headline price does not advertise.

With commercial insurance and a manufacturer savings card, either drug can land near $25 a month, at which point none of this arithmetic survives and the clinical questions are all that is left.

Side effects cluster after dose increases - log them that way

The most useful sentence in this entire comparison is the one from the tolerability section: side effects cluster in the weeks after a dose increase, not at steady state. That single fact converts nausea from a reason to quit into a scheduling problem - but only if you can see the pattern, and you cannot see a pattern you did not record.

The log that matters here is not a weight diary. It is side-effect severity plotted against the dose timeline. Three bad days after each escalation that resolve by day ten is a drug working normally and an argument for holding the current dose a little longer. Three bad weeks that never settle is a different conversation. Those two look identical in memory and completely different on a chart.

This is the axis our GLP-1 app ranking weights most heavily, because it is where the category most often fails. Zenday App takes the top spot at 4.55/5 for treating side-effect management as a core pillar rather than a symptom checklist - it turns the dose cycle into a week you can plan around rather than absorb, which is the difference between scheduling a hard Tuesday and being ambushed by one. Shotsy ties severity to the dose timeline explicitly and exports the result for a clinician.

Worth remembering why this matters more than the six-point efficacy gap: in SURMOUNT-5, 5.6% of semaglutide patients and 2.7% of tirzepatide patients stopped over gastrointestinal side effects, and in ordinary practice roughly half of everyone stops within a year. A drug you abandon has an efficacy of zero regardless of which column it sat in.

What the evidence does not show

• No comparison at current ceilings.SURMOUNT-5 used semaglutide 2.4 mg. Wegovy HD 7.2 mg reached 20.7% in STEP UP, statistically indistinguishable from Zepbound’s 20.2% in a different trial. Cross-trial arithmetic is not evidence, but it is enough to make the gap an open question rather than a settled one.
• No long-term comparative safety data. SURMOUNT-5 ran 72 weeks for drugs intended to be taken for years.
• No head-to-head on any hard outcome. Nobody has compared these two on heart attacks, strokes, or deaths.
• Nothing about how either performs after you stop. Weight regain after discontinuation is well documented for both, and roughly half of people who start this class stop within a year.

How to choose

• Weight loss is the whole goal: Zepbound. More result, better tolerated, cheaper per point.
• You have had a heart attack or stroke, or have established cardiovascular disease: Wegovy.
• You have MASH with fibrosis: Wegovy. It is the only one with the indication.
• You have moderate-to-severe sleep apnea: Zepbound. It is the only drug approved for it.
• You could not tolerate Wegovy: the SURMOUNT-5 dropout data says Zepbound is a reasonable next step rather than a harder one. See semaglutide to tirzepatide.
• Your plan covers Wegovy and not Zepbound: take the covered one. A drug you can afford for three years beats a better drug you abandon in month five - and switching from Zepbound to Wegovy covers what to expect if you are moving in that direction.

Method and sources

Efficacy figures are the treatment-regimen estimands from SURMOUNT-5, plus STEP UP, SELECT, and SURPASS-CVOT as published. Prices are US manufacturer self-pay rates from LillyDirect and NovoCare, read on 27 August 2026, and change frequently. We take no money from either manufacturer, run no affiliate links, and publish corrections sent to our contact page. For the molecules rather than the brands, see semaglutide vs tirzepatide. For the diabetes-labelled pair, see Mounjaro vs Ozempic.