Wegovy vs Zepbound

These are the two leading approved medicines for chronic weight management, and unusually for this field, they have been tested directly against each other. That trial is the most useful thing on this page.

Both are once weekly injections. Both are FDA approved. Neither is a compounded product.

The mechanical difference

Wegovy contains semaglutide. It acts on the GLP-1 receptor, one of the gut hormone pathways that signals fullness and slows how quickly the stomach empties.

Zepbound contains tirzepatide. It acts on two receptors, GLP-1 and GIP. That second pathway is the reason it is often described as a dual agonist, and it is the leading explanation for the difference in results.

Same class of medicine. Different number of levers.

The head to head trial

In 2025 the New England Journal of Medicine published a trial comparing tirzepatide with semaglutide directly for the treatment of obesity. Tirzepatide produced greater weight loss.

That is worth stating carefully. It does not mean semaglutide failed. It means that when the two were put in the same trial, under the same conditions, one produced more weight loss than the other.

The wider evidence points the same way. A 2025 meta-analysis of GLP-1 medicines for weight management put tirzepatide 15 mg at 17.8 percent average weight loss (95 percent confidence interval 16.3 to 19.3) at 72 weeks, and semaglutide 2.4 mg at up to 13.9 percent (11.0 to 16.7) at 68 weeks.

Note the different timeframes. Those are separate trials with separate designs, which is exactly why the head to head matters more than comparing two numbers from two studies.

What the individual trials showed

Semaglutide 2.4 mg, in its main obesity trial, produced average weight loss of 14.9 percent against 2.4 percent on placebo. 86.4 percent of participants reached at least 5 percent loss, 69.1 percent reached 10 percent, and 50.5 percent reached 15 percent.

Tirzepatide in its own obesity programme produced some of the largest average results seen in the class.

Where semaglutide has something tirzepatide does not

Cardiovascular outcome evidence. In the SELECT trial, semaglutide 2.4 mg reduced a combined endpoint of cardiovascular death, non-fatal heart attack and non-fatal stroke, with a hazard ratio of 0.80 (95 percent confidence interval 0.72 to 0.90). Over a mean of just under 40 months, 6.5 percent of the semaglutide group had an event against 8.0 percent on placebo.

If your reason for taking one of these is partly cardiovascular, that is a real difference in the evidence base and worth raising with a clinician.

Side effects

Broadly similar, and mostly gastrointestinal. Across GLP-1 trials, gastrointestinal events were reported by 47 to 84 percent of people on the medicine against 13 to 63 percent on placebo. Nausea, vomiting, diarrhoea and constipation are the common ones, and they cluster during the dose increase phase and settle over time.

Serious adverse events were rare in the trials, at 0 to 10 percent on the medicines against 0 to 12 percent on placebo.

Discontinuation because of side effects varied by trial, in the range of 0 to 26 percent against 0 to 9 percent on placebo. In SELECT, 16.6 percent of the semaglutide group stopped because of adverse events against 8.2 percent on placebo.

Both carry a boxed warning for thyroid C-cell tumours and are contraindicated for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.

Cost in 2026

This changed materially, and in a way that affects the comparison.

Both are named in the Medicare GLP-1 Bridge. CMS lists Wegovy, in injection and tablet form, and Zepbound KwikPen among the products available at fifty dollars a month for eligible Part D beneficiaries, from 1 July 2026 to 31 December 2027. The fine print: the Part D deductible does not apply, the fifty dollars does not count toward your true out of pocket total, and there is no low income subsidy attached.

Both are available at reduced cash prices through the federal direct purchasing channel launched in early 2026, for people without coverage.

So for a lot of people the choice is no longer strongly driven by price, which it was a year ago.

What happens if you stop

The same for both, and worth knowing before you start. A meta-analysis of 11 studies covering 12,539 people found that after stopping a high dose GLP-1 medicine, 50 to 65 percent of the weight lost came back within twelve months, with most of the regain in the first three to six months.

In the extension of semaglutide's main trial, people who stopped regained 67 percent of what they had lost within a year. In tirzepatide's withdrawal trial, people who stopped regained 14 percent of their starting body weight while those who continued lost more.

Neither of these is a short course. Plan on that basis.

So which one

On weight loss alone, the head to head favoured tirzepatide. On cardiovascular outcome evidence, semaglutide has the trial that tirzepatide does not. On side effects they are broadly comparable. On cost in 2026 they are closer than they have ever been.

That is genuinely a clinical conversation rather than a web page decision, because it turns on your history, your other conditions, and what your coverage actually pays for.

What to ask

• Given my history, is there a reason to prefer one of these over the other?
• Does my reason for taking this include cardiovascular risk?
• Which one does my plan actually cover, and at what dose?
• Am I eligible for the Medicare GLP-1 Bridge?
• What is the plan if I want to stop later?

Sources

• Tirzepatide as compared with semaglutide for the treatment of obesity. New England Journal of Medicine, 2025. doi:10.1056/NEJMoa2416394
• Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 2022. doi:10.1056/nejmoa2206038
• Once-weekly semaglutide in adults with overweight or obesity (STEP 1). New England Journal of Medicine, 2021
• Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). New England Journal of Medicine, 2023
• Efficacy and safety of GLP-1 receptor agonists for weight management, systematic review and meta-analysis, 2025
• Weight regain after discontinuation of high dose GLP-1 receptor agonists, meta-analysis of 11 studies, 2026
• Centers for Medicare and Medicaid Services, Medicare GLP-1 Bridge

How we verify: see /how-we-verify.

Keep reading

The molecule level comparison behind these two brands, at /guides/semaglutide-vs-tirzepatide.

Why Ozempic and Wegovy are not the same product, at /guides/ozempic-vs-wegovy.