Wegovy vs Zepbound

The head-to-head

SURMOUNT-5 randomised 751 adults with obesity and no diabetes to the maximum tolerated dose of either drug for 72 weeks. No placebo, open-label.

That last card is the caveat that matters. Each brand’s own placebo-controlled trials show how much the top dose has moved.

Wegovy 7.2 mg closes most of the gap on paper, 18.7% against 20.9%, but those are different trials with different populations, and STEP UP found dysaesthesia, altered skin sensation, in 22.9% of the 7.2 mg group versus 6% on 2.4 mg. Until someone runs tirzepatide against semaglutide 7.2 mg, the honest head-to-head answer is SURMOUNT-5’s.

The indications only one brand has

Wegovy: heart and liver. SELECT enrolled 17,604 adults with cardiovascular disease and obesity but no diabetes. Over a mean 40 months, 6.5% had a heart attack, stroke, or cardiovascular death on semaglutide 2.4 mg versus 8.0% on placebo, hazard ratio 0.80. That is the only cardiovascular outcomes trial of a weight-loss dose in people without diabetes, and it is on the Wegovy label. ESSENCE added MASH: combined resolution of steatohepatitis and fibrosis improvement in 32.7% versus 16.1% on placebo, an accelerated approval.

Zepbound: sleep apnea. SURMOUNT-OSA ran two 52-week trials in adults with moderate to severe obstructive sleep apnea and obesity. The apnea-hypopnea index fell by 25.3 events per hour on tirzepatide versus 5.3 on placebo in people not using a PAP machine, and by 29.3 versus 5.5 in people already on one. Zepbound became the first drug approved for the condition. It has no cardiovascular or liver indication; its diabetes sibling Mounjaro has a cardiovascular one from a trial in type 2 diabetes.

The dose ladders

Wegovy escalates on a four-week calendar, and the label allows a four-week delay at any step that is not tolerated. Zepbound holds each step at least four weeks and moves by tolerability. The milligram numbers are not comparable across the two molecules, which is why no conversion table exists.

Pens, vials, and a tablet

Wegovy ships as single-dose pens at every step, a 7.2 mg pen branded Wegovy HD, single-dose syringes, and a four-dose FlexTouch pen. Its label also covers a tablet in 1.5, 4, 9, and 25 mg, and in OASIS 4 the 25 mg tablet produced 13.6% weight loss over 64 weeks, close to the injection’s STEP 1 result.

Zepbound ships as a single-dose pen and, in the U.S., as single-dose vials drawn with a syringe. There is no tirzepatide tablet. Lilly’s oral GLP-1 is a different molecule, orforglipron.

What is identical

The safety sections. Both labels open with the boxed warning on thyroid C-cell tumors, both are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2, and both carry the same warnings on pancreatitis, gallbladder disease, severe gastrointestinal reactions, and acute kidney injury from dehydration. In SURMOUNT-5, adverse events in both groups were mostly gastrointestinal, mostly mild to moderate, and mostly during escalation. One difference sits in the drug-interactions section: the Zepbound label tells people on oral hormonal contraceptives to switch to a non-oral method or add a barrier method for four weeks after starting and after each dose increase; the Wegovy label has no such instruction.

The four-brand map

Same molecule, two names, so that each label carries only the indications its own trials support.

Which comparison you wanted

• The diabetes brands, with the SURPASS-2 head-to-head: Ozempic vs Mounjaro.
• The molecules across both indications: semaglutide vs tirzepatide.
• Why Wegovy and Ozempic are one drug: Ozempic vs Wegovy.
• Why Zepbound and Mounjaro are one drug: Zepbound vs Mounjaro.
• The approved pen against a pharmacy vial: Wegovy vs compounded semaglutide.

Whichever brand, the log entry is the same: product, date, milligrams, site. How GLP-1 tracking works covers what to record.

8. Wegovy vs Zepbound FAQ

• Which causes more weight loss, Wegovy or Zepbound?

  In SURMOUNT-5, the only direct trial, tirzepatide produced 20.2% mean weight loss over 72 weeks versus 13.7% for semaglutide at 2.4 mg. Wegovy's newer 7.2 mg dose produced 18.7% in STEP UP but was not part of that comparison. Which product is appropriate is a prescriber's decision and depends on more than the weight number.

• Does Zepbound lower heart attack risk like Wegovy?

  Wegovy carries a cardiovascular indication from SELECT, where major events fell from 8.0% to 6.5% in people with cardiovascular disease and obesity. Zepbound has no cardiovascular indication. Its diabetes sibling Mounjaro does, from SURPASS-CVOT, but that trial was in type 2 diabetes.

• Can I switch from Wegovy to Zepbound?

  Switching between molecules is a prescriber decision. There is no conversion table; each label starts at its own first step, 0.25 mg for Wegovy and 2.5 mg for Zepbound. Neither label addresses switching from the other.

• Which has fewer side effects?

  Both labels carry the same boxed warning and the same gastrointestinal, pancreatitis, and gallbladder warnings. In SURMOUNT-5, the most common adverse events in both groups were gastrointestinal, mostly mild to moderate and mostly during dose escalation. The trial did not find one product clearly better tolerated.

• Is there a Zepbound pill?

  No. Wegovy has an approved tablet, up to 25 mg, on its own label. Tirzepatide has no oral form; Lilly's oral GLP-1 is a different molecule, orforglipron, sold as Foundayo.

9. Sources