Semaglutide vs tirzepatide: how Wegovy and Zepbound compare on weight loss, side effects and dosing

What is the difference between semaglutide and tirzepatide?

Semaglutide and tirzepatide are the two medicines behind most of today’s GLP-1 prescriptions. They are taken the same way, a once-weekly injection, and both reduce appetite and help you feel full sooner. The difference is in how many hormone receptors they act on.

• Semaglutide is a GLP-1 receptor agonist. It mimics one gut hormone, GLP-1. In the US it is sold as Wegovy (weight, heart risk and MASH) and Ozempic (type 2 diabetes), and both now also come as tablets, alongside Rybelsus.
• Tirzepatide is a single molecule that activates two receptors, GIP and GLP-1, according to its prescribing information. It is sold as Zepbound (weight and sleep apnea) and Mounjaro (type 2 diabetes).

A dual mechanism doesn’t automatically make a medicine “better” for every person. It’s one reason the two were compared directly in a trial, and that trial is the best place to start.

Which causes more weight loss: Wegovy or Zepbound?

The clearest answer comes from SURMOUNT-5, published in the New England Journal of Medicine in 2025. It randomly assigned 751 adults with obesity but without type 2 diabetes to the highest dose each person could tolerate of either tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks. Both groups also had lifestyle counseling.

In kilograms, that was an average of about 22.8 kg on tirzepatide and 15.0 kg on semaglutide. Waist circumference fell by 18.4 cm and 13.0 cm. More people on tirzepatide reached each weight-loss milestone the trial measured (10%, 15%, 20% and 25%).

A few things are worth keeping in mind:

• Open-label design. Participants knew which medicine they were taking.
• Who was studied. People with type 2 diabetes were excluded. In diabetes, an earlier head-to-head trial, SURPASS-2, compared tirzepatide with semaglutide 1 mg (an Ozempic dose) over 40 weeks and found larger HbA1c and weight reductions with all three tirzepatide doses.
• Dose range. SURMOUNT-5 used semaglutide up to 2.4 mg. The Wegovy label now also allows 7.2 mg for some adults. In the separate STEP UP trial, 7.2 mg led to −18.7% versus −15.6% on 2.4 mg, but it hasn’t been compared with tirzepatide.

What did the original placebo-controlled trials show?

Before any head-to-head data, each medicine had its own pivotal trial. These are different trials with different people and durations, so don’t compare the numbers directly:

• STEP 1 (semaglutide 2.4 mg, 68 weeks): −14.9% average weight change vs −2.4% on placebo.
• SURMOUNT-1 (tirzepatide, 72 weeks): −15.0% on 5 mg, −19.5% on 10 mg and −20.9% on 15 mg vs −3.1% on placebo.

Both drugs led to substantial weight loss compared with placebo. SURMOUNT-5 is what lets us compare them side by side.

Semaglutide vs tirzepatide at a glance

The nausea figures come from each drug’s own placebo-controlled trials, listed in the labels. They used different escalation schedules and populations, so they hint at a difference but aren’t a direct comparison.

Are tirzepatide and semaglutide side effects different?

The side-effect profiles look more alike than different. Both labels list nausea, diarrhea, vomiting, constipation and abdominal pain among the most common reactions, and in SURMOUNT-5 GI events were the most common in both groups, mostly mild to moderate and mainly during dose escalation.

Where SURMOUNT-5 did show a gap was in stopping treatment: 2.7% of people on tirzepatide and 5.6% on semaglutide stopped because of GI side effects. That’s one trial, and your own tolerance can’t be predicted from it. If nausea is the main problem, our guide to GLP-1 nausea relief covers practical steps.

The serious warnings are shared. Both labels carry a boxed warning about thyroid C-cell tumors seen in rodents and are not for people with a personal or family history of medullary thyroid carcinoma or MEN 2. Both list pancreatitis, gallbladder disease and kidney injury from dehydration.

One practical difference: the Zepbound label advises people using oral birth-control pills to switch to a non-oral method, or add a barrier method, for 4 weeks after starting and after each dose increase. The Wegovy label has no such advice. See GLP-1s, birth control and pregnancy for details.

How do the dosing schedules compare?

Both start low and step up no sooner than every 4 weeks to limit side effects:

• Wegovy: 0.25, 0.5, 1 and 1.7 mg, then 2.4 mg (or 1.7 mg) from week 17. For adult weight reduction, 7.2 mg is possible after at least 4 weeks on 2.4 mg if more weight loss is clinically indicated.
• Zepbound: 2.5 mg for 4 weeks (a starting dose only), then 5 mg, rising in 2.5 mg steps to a maintenance dose of 5, 10 or 15 mg.

Our GLP-1 dose escalation schedule lays out every step, including Ozempic and Mounjaro. Reaching the top dose isn’t the goal in itself; both labels ask prescribers to weigh response and tolerability.

Which GLP-1 is better for you?

There’s no single “better” GLP-1. The labels and your health history narrow the choice, and that’s a conversation for your doctor. Factors that often come up:

Approved uses

• Established heart disease with overweight or obesity: Wegovy has a heart-risk indication in this group.
• Obstructive sleep apnea with obesity: Zepbound is approved for moderate to severe OSA.
• MASH (fatty liver disease) with moderate to advanced fibrosis: Wegovy has an accelerated approval.
• Type 2 diabetes: Ozempic and Mounjaro are the diabetes brands, and both have a heart-risk indication for some adults with diabetes. Ozempic also has a kidney indication for adults with type 2 diabetes and chronic kidney disease.
• Teenagers: Wegovy is approved for weight reduction from age 12. Zepbound’s pediatric safety hasn’t been established.

How much weight loss matters for your goals

SURMOUNT-5 showed larger average loss with tirzepatide. For some people, a smaller loss with fewer side effects, or a medicine that also covers another condition, may matter more.

Side effects you’ve already had

If you’ve struggled with one medicine, your prescriber may consider a different dose or a different medicine. Our guide to switching GLP-1 medications explains what that usually involves.

Cost and access

Prices, insurance coverage and supply differ by country, plan and indication. A plan may cover one brand for diabetes but not the other for weight. Ask your pharmacist or insurer early, so the decision isn’t made on efficacy alone.

When should you call your doctor?

Whichever medicine you take, contact your care team promptly, or get urgent help, if you notice:

• Severe stomach pain that won’t go away, sometimes spreading to your back, with or without vomiting (possible pancreatitis)
• Pain in your upper stomach, fever, yellow skin or eyes, or clay-colored stools (possible gallbladder problems)
• Vomiting or diarrhea that stops you keeping fluids down, dizziness or passing very little urine (possible dehydration and kidney strain)
• Swelling of the face, lips, tongue or throat, or trouble breathing or swallowing (possible serious allergic reaction)
• A lump in the neck, trouble swallowing, shortness of breath or lasting hoarseness (possible thyroid tumor symptoms listed in both labels)
• Signs of low blood sugar if you also take insulin or a sulfonylurea

Making the comparison personal

Trial averages tell you what happened to groups. What matters is how your weight, side effects and energy respond on the medicine you’re actually taking. GLPMate keeps your dose log with reminders, a side-effect log with severity and your weight trend in one place, whether you’re on semaglutide or tirzepatide, and turns it into a doctor report (PDF) you can bring to your next appointment.

This article is educational only and not medical advice. Talk to your doctor before starting, switching or changing any GLP-1 medicine.

FAQ

FAQ

Is tirzepatide better than semaglutide for weight loss?

In SURMOUNT-5, adults with obesity but without diabetes lost an average of 20.2% of body weight on tirzepatide versus 13.7% on semaglutide after 72 weeks. Those are averages from one open-label trial funded by tirzepatide's maker, and individual results vary widely. Which medicine suits you also depends on side effects, other health conditions and coverage.

Does tirzepatide have fewer side effects than semaglutide?

Both labels list nausea, diarrhea, vomiting and constipation as the most common side effects, mostly during dose escalation. In SURMOUNT-5, 2.7% of people on tirzepatide and 5.6% on semaglutide stopped because of GI side effects. That is one trial, and how you personally tolerate either medicine can't be predicted in advance.

Can I switch from semaglutide to tirzepatide?

Yes, people do switch, but neither label sets out a conversion from the other medicine, so your prescriber chooses the starting dose and timing. The Wegovy and Zepbound labels advise against using them together with another GLP-1 medicine. Don't stop one and start the other on your own.

Which GLP-1 is approved for heart disease or sleep apnea?

In the US, Wegovy is approved to lower the risk of heart attack, stroke and cardiovascular death in adults with established heart disease and overweight or obesity, and Zepbound is approved for moderate to severe obstructive sleep apnea in adults with obesity. Ozempic and Mounjaro have heart-risk indications for people with type 2 diabetes. Labels change, so ask your doctor about the current one.