Wegovy vs Zepbound — Uses, Doses and the SURMOUNT-5 Trial

Your insurance covers one of them, your friend is on the other, and your prescriber has said either could be reasonable. Somewhere between the pharmacy call and the coverage letter, you would like a plain picture of how Wegovy and Zepbound actually differ. Here it is, from the labels and the one trial that compared them directly.

What is each one approved for?

Both are approved, with a reduced-calorie diet and more physical activity, to reduce excess body weight and keep it off long term in adults with obesity, or with overweight plus a weight-related condition. Beyond that, each has its own list.

Wegovy (semaglutide) injection is also approved to lower the risk of heart attack, stroke and heart-related death in adults with established heart disease and obesity or overweight; for adolescents 12 and older with obesity; and, under accelerated approval, for a form of fatty liver disease called MASH with moderate to advanced fibrosis. Wegovy tablets cover weight reduction and heart risk reduction in adults.

Zepbound (tirzepatide) is also approved to treat moderate to severe obstructive sleep apnea in adults with obesity.

If one of those extra conditions applies to you, it is likely to shape your prescriber's thinking.

What did SURMOUNT-5 find?

SURMOUNT-5 is the head-to-head trial. It randomized 751 adults with obesity and without type 2 diabetes to the highest dose they could tolerate of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg), once weekly for 72 weeks. It was open-label and funded by Lilly, which makes Zepbound.

• Average weight change: −20.2% with tirzepatide, −13.7% with semaglutide.
• Average waist change: −18.4 cm and −13.0 cm.
• Larger reductions: more people on tirzepatide reached weight reductions of at least 10%, 15%, 20% and 25%.

Those are group averages. Plenty of people on each medicine landed well above or below them. The trial also predates Wegovy's 7.2 mg dose, so it does not tell us how that dose would compare.

How do the dose schedules differ?

Both start low and climb slowly to limit stomach side effects, but the steps look different.

Wegovy injection moves through 0.25, 0.5, 1 and 1.7 mg, each for 4 weeks, reaching a maintenance dose of 1.7 or 2.4 mg from week 17. For adults using it for weight reduction who have tolerated 2.4 mg for at least 4 weeks, the label allows an increase to 7.2 mg. Wegovy tablets start at 1.5 mg daily and step up every 30 days to 25 mg.

Zepbound starts at 2.5 mg for 4 weeks and increases in 2.5 mg steps, at least 4 weeks apart. Maintenance is 5, 10 or 15 mg for weight, and 10 or 15 mg for sleep apnea.

Pens, vials, syringes or a tablet?

Wegovy injection comes as single-dose pens and single-dose syringes, and Wegovy is the one with a daily tablet. Zepbound comes as single-dose pens, single-dose vials, multi-dose vials and a four-dose KwikPen; it has no tablet.

Missed doses work differently too. For a missed Wegovy injection, the label says take it if your next dose is more than 2 days away, otherwise skip it. For Zepbound, take it within 4 days, otherwise skip it.

How do side effects compare?

Both labels list stomach side effects — nausea, diarrhea, vomiting, constipation, stomach pain — as the most common, mostly during dose increases. In SURMOUNT-5, gastrointestinal events were the most common in both groups and were mostly mild to moderate.

Each label has its own extras. Zepbound's lists injection-site reactions, fatigue and hair loss among common effects. Wegovy's lists headache, dizziness and dysesthesia — unusual skin sensations, which the label says became more frequent at higher doses, at 22% on 7.2 mg. Both carry similar warnings, including a boxed warning about thyroid tumors seen in rodents.

What we'd track

On either medicine, here is what we would write down.

1. Medicine, form and dose. Pen, vial, syringe or tablet — the missed-dose rule depends on it.
2. Every dose with the time. For tablets, a daily tick; for injections, the weekly shot and its site.
3. Side effects against dose steps. To see whether symptoms settle as the labels describe.
4. Weight trend and waist. Weekly is plenty, and calmer than daily.
5. Sleep notes, if you have sleep apnea. How rested you feel is useful context for your sleep doctor.

Holt logs shots or pills with reminders and a Live Activity, tracks injection sites, meals, water and weight with Apple Health sync, and builds a doctor-visit report on your iPhone. It is free to download, with an optional subscription.

Track Wegovy or Zepbound in Holt