Zepbound vs Wegovy: Differences From the FDA Labels and Trials

Zepbound and Wegovy are both weekly shots approved for weight management in the US, but they’re different molecules. Zepbound is tirzepatide, made by Eli Lilly, which activates two gut-hormone receptors, GIP and GLP-1^[1]. Wegovy is semaglutide, made by Novo Nordisk, which activates the GLP-1 receptor^[2]. In the only head-to-head trial, SURMOUNT-5, weight fell 20.2% on tirzepatide and 13.7% on semaglutide over 72 weeks^[3]. Beyond weight, their labels go in different directions: sleep apnea for Zepbound, heart risk and a liver disease for Wegovy^[1,2]. Which one fits a given person is your prescriber’s call.

In 30 seconds

Zepbound is approved for weight reduction and long-term maintenance in adults with obesity, or overweight with at least one weight-related condition, and for moderate to severe obstructive sleep apnea in adults with obesity^[1].
Wegovy injection is approved for lowering the risk of heart attack, stroke and cardiovascular death in adults with established cardiovascular disease and obesity or overweight; weight reduction in adults and in children 12 and older with obesity; and noncirrhotic MASH with moderate to advanced liver fibrosis in adults^[2].
SURMOUNT-5 (751 adults without diabetes, 72 weeks): −20.2% weight on tirzepatide vs. −13.7% on semaglutide, a difference of 6.5 points^[3].
Nausea in SURMOUNT-5: 43.6% on tirzepatide and 44.4% on semaglutide; vomiting, 15.0% and 21.3%^[4].
Birth-control pills: the Zepbound label advises a non-oral method, or adding a barrier method, for 4 weeks after starting and after each dose increase^[1]. The Wegovy label has no such advice^[2].

If you’re comparing brands of the same molecule, I have Mounjaro vs. Zepbound (both tirzepatide) and Ozempic vs. Wegovy (both semaglutide). The diabetes brands go head to head in Ozempic vs. Mounjaro.

Zepbound vs. Wegovy at a glance

	Zepbound	Wegovy
Active ingredient and maker	Tirzepatide (Eli Lilly)	Semaglutide (Novo Nordisk)
Receptors it activates	GIP and GLP-1	GLP-1
First FDA approval for weight	November 8, 2023	June 4, 2021
Other US-approved uses	Moderate to severe obstructive sleep apnea in adults with obesity	Cardiovascular risk reduction; MASH with moderate to advanced fibrosis (injection, accelerated approval)
Ages on the label	Adults	Adults; children 12 and older with obesity (injection)
Highest weekly dose	15 mg	7.2 mg, for weight in adults
Forms	Single-dose pens and vials, 4-dose multi-dose vials and KwikPens	Single-dose pens (7.2 mg as Wegovy HD), a 4-dose FlexTouch pen of 2.4 mg, single-dose syringes, and daily tablets
Boxed warning	Thyroid C-cell tumors in rodents	Thyroid C-cell tumors in rodents

Sources: boxed warnings and sections 1, 2 and 3 of the US labels for Zepbound^[1] and Wegovy^[2]; approval dates from the FDA^[10] and Drugs@FDA^[12].

What each one is approved for

Both labels approve weight management in the same adults: adults with obesity, or adults with overweight and at least one weight-related condition, alongside a reduced-calorie diet and more physical activity^[1,2]. The rest differs:

Sleep apnea: Zepbound only. The FDA added moderate to severe obstructive sleep apnea in adults with obesity to Zepbound’s label in December 2024^[1,11]. I cover it in Zepbound for sleep apnea.
Heart risk: Wegovy only. Wegovy’s label covers reducing the risk of cardiovascular death, nonfatal heart attack or nonfatal stroke in adults with established cardiovascular disease and either obesity or overweight^[2], a use approved in March 2024^[13].
Liver disease: Wegovy only. The injection is approved for noncirrhotic MASH with moderate to advanced liver fibrosis (stages F2 to F3) in adults, under accelerated approval^[2]. MASH, metabolic dysfunction-associated steatohepatitis, is fatty liver disease with inflammation. Accelerated approval means continued approval may depend on a confirmatory trial^[2].
Teens: Wegovy only. Wegovy injection covers pediatric patients aged 12 years and older with obesity^[2]. The Zepbound label says safety and effectiveness have not been established in pediatric patients^[1].
A pill: Wegovy only. Wegovy also comes as a daily tablet, approved in December 2025^[14], for weight and heart risk in adults^[2].

SURMOUNT-5: the head-to-head trial

SURMOUNT-5 enrolled 751 adults with obesity, or with overweight and at least one weight-related complication, without diabetes^[3]. Each group got the highest dose they tolerated: tirzepatide 15 or 10 mg, or semaglutide 2.4 or 1.7 mg, once weekly, for 72 weeks^[3]. According to the registry, 196 of the 750 participants with data, about one in four, were Hispanic or Latino^[4].

At 72 weeks	Tirzepatide (Zepbound)	Semaglutide (Wegovy)	Difference (95% CI)
Average weight change	−20.2%	−13.7%	−6.5 points (−8.1 to −4.9)
Average waist change	−18.4 cm	−13.0 cm	—

Source: trial paper^[3]. A 95% CI (confidence interval) is the likely range of the true effect.

More people on tirzepatide reached weight losses of at least 10%, 15%, 20% and 25%^[3]. The side effects, from the registry, in everyone who got at least one dose:

Side effect over 72 weeks	Tirzepatide (374 people)	Semaglutide (376 people)
Nausea	43.6%	44.4%
Constipation	27.0%	28.5%
Diarrhea	23.5%	23.4%
Vomiting	15.0%	21.3%
Serious adverse events	4.8%	3.5%

Source: SURMOUNT-5 registry results^[4]. Percentages per side effect count non-serious events.

The limits matter. The trial was open-label: people knew which drug they were getting, which can affect adherence and what gets reported^[3]. Eli Lilly, Zepbound’s maker, funded it, and there was no placebo group^[3]. It excluded people with diabetes, didn’t test Wegovy’s 7.2 mg dose and didn’t measure heart attacks or strokes^[3]. Vomiting was less common on tirzepatide, but the registry doesn’t report a statistical test for that difference^[4].

STEP 1 and SURMOUNT-1: each against placebo

Before SURMOUNT-5, each drug was tested against placebo in adults without diabetes:

STEP 1 (1,961 adults, 68 weeks): weight fell 14.9% on semaglutide 2.4 mg vs. 2.4% on placebo (paper)^[5].
SURMOUNT-1 (2,539 adults, 72 weeks): weight fell 15.0%, 19.5% and 20.9% on tirzepatide 5, 10 and 15 mg vs. 3.1% on placebo (paper)^[6].

Don’t subtract one from the other to pick a winner: the trials differ in length, population and timing. That’s what SURMOUNT-5 is for. The trial results chart puts them side by side.

Heart, sleep apnea and liver: the outcome trials

Each brand’s extra uses rest on a different trial:

Wegovy and the heart: SELECT. 17,604 adults with established cardiovascular disease and a BMI of 27 or more, without diabetes^[7]. Over a mean follow-up of 39.8 months, a heart attack, stroke or cardiovascular death happened in 6.5% on semaglutide 2.4 mg vs. 8.0% on placebo (hazard ratio 0.80; 95% CI 0.72 to 0.90) (paper)^[7].
Wegovy and the liver: ESSENCE. In the first 800 adults with MASH and stage 2 or 3 fibrosis, at 72 weeks, steatohepatitis resolved without worsening fibrosis in 62.9% on semaglutide 2.4 mg vs. 34.3% on placebo (paper)^[9].
Zepbound and sleep apnea: SURMOUNT-OSA. 469 adults with moderate to severe sleep apnea and obesity, without diabetes^[8]. At 52 weeks, breathing interruptions per hour of sleep (the apnea-hypopnea index) fell by 25.3 vs. 5.3 on placebo in people not using CPAP, and by 29.3 vs. 5.5 in people using it (paper)^[8].

Tirzepatide’s published heart-outcomes trial, SURPASS-CVOT, isn’t a weight trial: it compared tirzepatide with dulaglutide, another GLP-1 drug, in 13,299 adults with type 2 diabetes and cardiovascular disease. Over a median of 4 years, a heart attack, stroke or cardiovascular death happened in 12.2% vs. 13.1% (hazard ratio 0.92; 95.3% CI 0.83 to 1.01): tirzepatide was not worse, but wasn’t shown to be better (paper)^[15].

No trial has compared the two on heart attacks, strokes, sleep apnea or liver outcomes. SELECT tested semaglutide, so its result can’t be assumed for tirzepatide, and SURMOUNT-OSA’s can’t be assumed for semaglutide^[7,8].

Doses and devices

Both are weekly injections under the skin, started low and raised step by step to reduce digestive side effects^[1,2]:

	Zepbound	Wegovy injection
Starting dose	2.5 mg once weekly for 4 weeks; not a maintenance dose	0.25 mg once weekly, weeks 1 to 4
Steps	5 mg after 4 weeks; then 2.5 mg increases after at least 4 weeks on the current dose	0.5, 1 and 1.7 mg, 4 weeks each, through week 16
Maintenance	5, 10 or 15 mg for weight; 10 or 15 mg for sleep apnea	2.4 mg (recommended) or 1.7 mg for weight and heart risk; 2.4 mg for MASH
Above that	15 mg is the maximum for all uses	Up to 7.2 mg in adults who tolerate 2.4 mg for at least 4 weeks and for whom more weight reduction is clinically indicated

Source: section 2 of the US labels for Zepbound^[1] and Wegovy^[2].

On missed doses the labels differ. Zepbound’s says to take it within 4 days (96 hours) and, after that, skip it^[1]. Wegovy’s says to take it if the next dose is more than 2 days away and otherwise skip it, and to restart the escalation at a lower dose after 2 or more consecutive missed doses^[2]. What to do in your case is for your prescriber to confirm.

A milligram of tirzepatide isn’t a milligram of semaglutide, and neither label offers a conversion. Which product, which dose and when to change it is your prescriber’s decision.

Side effects, warnings and pregnancy

Side effects in each label

Each label reports its own placebo-controlled trials, so read the columns as context, not as a ranking. The fair comparison, in the same trial, is the SURMOUNT-5 table above.

Side effect (placebo in parentheses)	Zepbound 5 / 10 / 15 mg	Wegovy 2.4 mg
Nausea	25% / 29% / 28% (8%)	44% (16%)
Diarrhea	19% / 21% / 23% (8%)	30% (16%)
Vomiting	8% / 11% / 13% (2%)	24% (6%)
Constipation	17% / 14% / 11% (5%)	24% (11%)
Hair loss	5% / 4% / 5% (1%)	3% (1%)

Source: section 6.1 of the US labels for Zepbound (Table 1, SURMOUNT-1 and SURMOUNT-2)^[1] and Wegovy (Table 3, weight-management trials)^[2].

If digestive side effects are the problem, I have guides on what to eat with nausea and on side effects week by week. Anything that worries you is worth raising with your doctor.

Warnings and who shouldn’t use them

Both labels carry the same boxed warning and the same contraindications: thyroid C-cell tumors in rodents, of unknown relevance to humans; not for people with a personal or family history of medullary thyroid carcinoma or with MEN 2, or with a serious hypersensitivity to the drug^[1,2]. Both warn about acute pancreatitis, gallbladder disease, low blood sugar with insulin or sulfonylureas, kidney injury from dehydration, severe digestive reactions, diabetic retinopathy complications and aspiration during anesthesia or deep sedation^[1,2]. Both say they aren’t recommended with other GLP-1 receptor agonists^[1,2].

Pregnancy, breastfeeding and birth control

	Zepbound	Wegovy
Pregnancy	Discontinue when a pregnancy is recognized	Discontinue at least 2 months before a planned pregnancy; for weight or heart risk, discontinue when a pregnancy is recognized
Breastfeeding	Weigh the benefits of breastfeeding against the need for the drug	Injection: weigh benefits and need; tablets: breastfeeding not recommended
Birth-control pills	May work less well; switch to a non-oral method, or add a barrier method, for 4 weeks after starting and after each dose increase	No advice on oral contraceptives in the label

Source: sections 7 and 8 of the US labels for Zepbound^[1] and Wegovy^[2].

The birth-control difference is real and practical. The Zepbound label explains that delayed stomach emptying can lower the effect of oral contraceptives, most after the first dose^[1]. If you use the pill, ask your prescriber how that applies to you.

Price, and why I don’t rank them

I keep list prices, with their sources and dates, in the monthly cost calculator, which also has Wegovy. The per-brand details are in Mounjaro vs. Zepbound and Ozempic vs. Wegovy. What you pay depends on your plan, and a plan may cover one for a specific approved use and not the other. Cheaper wouldn’t make them interchangeable.

Which is better?

There isn’t one answer for everyone. Here’s what the evidence supports:

Average weight loss. Tirzepatide lowered average weight more than semaglutide 2.4 mg in SURMOUNT-5^[3]. An average doesn’t predict what will happen to one person, and the trial didn’t test Wegovy’s 7.2 mg dose^[3].
Tolerability. In the same trial, nausea and diarrhea were similar, with less vomiting on tirzepatide^[4].
Other conditions. Wegovy has approved uses for heart risk and MASH; Zepbound, for sleep apnea^[1,2].
Specific situations. Age, pregnancy plans, the pill or type 2 diabetes change what each label says^[1,2].

Putting that together with your history and your other medicines is your prescriber’s job. More background in the tirzepatide guide and the semaglutide guide.

Frequently asked questions

Can you switch from Wegovy to Zepbound?

That’s a decision for your prescriber. Neither label describes switching from one to the other or gives a dose conversion^[1,2]. The Wegovy label only covers switching between Wegovy injection and Wegovy tablets^[2]. Both labels say not to combine them with another GLP-1 receptor agonist^[1,2].

Is Zepbound stronger than Wegovy?

For average weight loss, yes, in SURMOUNT-5: 20.2% vs. 13.7% over 72 weeks, a 6.5-point difference^[3]. No published trial has compared tirzepatide with Wegovy’s 7.2 mg dose. “Stronger” isn’t the same as “better for you.”

Which has fewer side effects, Zepbound or Wegovy?

The data don’t show that one is better tolerated. In SURMOUNT-5, nausea affected 43.6% on tirzepatide and 44.4% on semaglutide, and vomiting 15.0% and 21.3%^[4]. Serious adverse events were 4.8% and 3.5%^[4]. In an open-label trial, knowing what you’re taking can shape what gets reported^[3].

Is Zepbound or Wegovy approved for sleep apnea?

Zepbound is, for moderate to severe obstructive sleep apnea in adults with obesity, with a maintenance dose of 10 or 15 mg^[1]. Wegovy’s label has no sleep apnea use^[2]. The details, including what SURMOUNT-OSA showed, are in Zepbound for sleep apnea.