Wegovy vs. Zepbound: Which Works Better?

Wegovy (semaglutide) and Zepbound (tirzepatide) are both once-weekly injections for long-term weight management. This guide covers how they're alike, how they differ, and what the one study that compared them directly found. It doesn't replace a conversation with your own prescriber, who can help you decide which fits your health and goals.

How These Medicines Work

Both are a small injection under the skin once a week. Both work mainly by lowering appetite, helping you feel full sooner, and slowing how quickly the stomach empties. They're used along with a reduced-calorie diet and more physical activity, not instead of them.[10][11]

• Semaglutide (Wegovy) acts on one gut-hormone pathway, called GLP-1.
• Tirzepatide (Zepbound) acts on two pathways at once, GLP-1 and GIP. Acting on both may be part of why it tends to produce more weight loss.[7]

Wegovy was approved for weight management in 2021, and Zepbound in November 2023.[8]

Both are meant to be taken long-term. Weight tends to come back after stopping either one, so they're best thought of as ongoing treatment for a long-term condition — see what happens when you stop.

How They Are Taken

Both start at a low dose that is slowly increased over several months. Starting low and going up gradually reduces nausea and other stomach side effects.[5][6]

	Wegovy (semaglutide)	Zepbound (tirzepatide)
How it's given	Injection under the skin	Injection under the skin
How often	Once a week	Once a week
Starting dose	0.25 mg per week	2.5 mg per week
How the dose goes up	About every 4 weeks	About every 4 weeks
Usual maintenance dose	1.7 or 2.4 mg per week; up to 7.2 mg for some adults	5, 10, or 15 mg per week
Time to reach 2.4 mg / full dose	About 4 months	About 4–5 months
Where to inject	Belly, thigh, or upper arm	Belly, thigh, or upper arm
When to take it	Any time of day, with or without food	Any time of day, with or without food
Device	Single-dose pen	Single-dose pen or vial, or KwikPen

Full schedules: Wegovy dosing and Zepbound dosing.

How Much Weight People Lose

In separate studies, both medicines led to meaningful weight loss over about 68–72 weeks (roughly a year and a half). With semaglutide 2.4 mg, people in the main study lost about 15% of their starting body weight on average.[3] With tirzepatide at the highest dose, people lost about 21% on average.[4]

Those were separate studies with different participants, so the numbers can't be compared directly — which is why a head-to-head trial mattered.

The Head-to-Head Study: SURMOUNT-5

The strongest evidence comes from SURMOUNT-5, published in the New England Journal of Medicine in 2025 — the first large trial to compare the two medicines directly.[1][2]

Who was in it: 751 adults with obesity, or overweight with a weight-related health problem, who did not have type 2 diabetes. Participants weighed about 249 lbs (113 kg) on average at the start.

What was done: people were randomly assigned to tirzepatide or semaglutide, each raised to the highest dose they could tolerate, for 72 weeks, along with diet and exercise changes.

What was found: tirzepatide led to more weight loss than semaglutide.

Result at 72 weeks	Tirzepatide (Zepbound)	Semaglutide (Wegovy)
Average weight loss	About 20% of body weight	About 14% of body weight
Average pounds lost	About 50 lbs (22.8 kg)	About 33 lbs (15.0 kg)
Lost at least 10% of weight	About 82 of 100 people	About 61 of 100 people
Lost at least 15% of weight	About 65 of 100 people	About 40 of 100 people
Lost at least 25% of weight	About 32 of 100 people	About 16 of 100 people
Reduction in waist size	About 7.2 inches (18.4 cm)	About 5.1 inches (13.0 cm)

The difference — about 6–7 percentage points more weight loss with tirzepatide — was statistically significant, meaning it was very unlikely to be due to chance.

What to keep in mind about this study:

• It was open-label: patients and their doctors knew which medicine was being used, which can affect results.
• It was paid for by the company that makes tirzepatide.
• It lasted about a year and a half, so it doesn't show differences over many years.
• Semaglutide was dosed up to 2.4 mg; the study did not test the newer 7.2 mg Wegovy dose.

Even so, the findings agree with what the earlier separate studies suggested.

Side Effects

Both medicines have a similar pattern of side effects. The most common ones affect the stomach and digestion, are usually mild to moderate, and are most noticeable while the dose is being increased.

Common side effects of both: nausea, diarrhea, vomiting, constipation, and stomach pain. Others include burping, heartburn, tiredness, headache, and some hair thinning.

In the head-to-head study the two had similar overall safety, and relatively few people stopped because of side effects — about 6 of 100 with tirzepatide and 8 of 100 with semaglutide. Redness or irritation at the injection site was more common with tirzepatide.[1]

What helps: eat smaller meals, stop eating when you're full, avoid very greasy or very large meals, and stay hydrated. Tell your prescriber if side effects are severe or don't improve — the dose can be increased more slowly. More: managing nausea on GLP-1s.

Serious Risks and Who Should Not Take These

Both medicines carry the same serious warnings, and both should be prescribed and monitored by a clinician.[5][6]

• Do not use either medicine if you or a close family member has had medullary thyroid carcinoma, or you have multiple endocrine neoplasia type 2 (MEN2). Both carry a warning about thyroid tumors based on animal studies.
• Do not use if you've had a serious allergic reaction to the medicine.
• Tell your prescriber if you've had pancreatitis, gallbladder problems, severe stomach or digestion problems, or kidney disease.
• Seek medical care for severe, ongoing stomach pain, signs of a serious allergic reaction, or being unable to keep fluids down.
• Pregnancy: neither medicine is for use in pregnancy. Tirzepatide can affect how birth control pills are absorbed, so a backup method is advised for 4 weeks after starting and after each dose increase — see birth control during GLP-1 dose escalation.
• Before surgery or a procedure with anesthesia, tell your care team you take one of these medicines, because they slow stomach emptying.

Heart Health

Wegovy has proven heart benefits. It's FDA-approved to lower the risk of heart attack, stroke, and cardiovascular death in adults with established heart disease and either obesity or overweight.[5]

For Zepbound, this is still being studied. Trials looking at heart attack and stroke in people with obesity are ongoing, so the benefit hasn't yet been proven for it. Zepbound does have one approval Wegovy doesn't: moderate-to-severe obstructive sleep apnea in adults with obesity.[6]

Questions to Ask Your Prescriber

• Which of these is a better fit for my health history and goals?
• What does my insurance cover, and what will it cost?
• How should I manage side effects if they happen?
• How long will I likely stay on this medicine?
• What should I do if I miss a dose or need to stop?

The Short Version

Both Wegovy and Zepbound are effective once-weekly injections for long-term weight management, used together with diet and activity changes. In the one study that compared them directly, Zepbound produced more weight loss over about a year and a half, with similar overall safety. Wegovy has proven heart benefits for certain people, which is still being studied for Zepbound. The better choice depends on your health history, other conditions, coverage and cost, and your own preferences — which is how obesity-medicine guidelines recommend choosing between them.[9] Thinking about changing from one to the other? See switching between semaglutide and tirzepatide.