Tirzepatide vs Semaglutide: Which Works Better for Weight Loss?

Sources for each row: the prescribing information for Wegovy, Ozempic, Rybelsus, Zepbound and Mounjaro, and the STEP 1, SURMOUNT-1 and SURMOUNT-5 trials.1,3,4,5,6,7,8,9

Semaglutide is a GLP-1 receptor agonist; tirzepatide acts on two receptors, GIP and GLP-1. The FDA labels describe Wegovy and Ozempic as glucagon-like peptide-1 (GLP-1) receptor agonists, and Zepbound and Mounjaro as glucose-dependent insulinotropic polypeptide (GIP) receptor and GLP-1 receptor agonists.5,7

Both mimic gut hormones that the body releases after eating. In practice, both slow digestion, reduce appetite and lower blood sugar. The extra GIP activity is the main pharmacological difference, and it is the reason tirzepatide is often called a "dual agonist." The two are not meant to be taken together: both the Zepbound and Wegovy labels say coadministration with any other GLP-1 receptor agonist is not recommended.5,7

If you have seen a "triple agonist" mentioned, that is retatrutide, an investigational drug that adds a third receptor. We cover it in GLP-3 and retatrutide, explained.

Semaglutide is sold as Wegovy, Ozempic and Rybelsus; tirzepatide is sold as Zepbound and Mounjaro. The difference between the brands is the approved use, not the molecule.

• Wegovy (semaglutide) is approved for chronic weight management, to reduce the risk of major cardiovascular events in adults with cardiovascular disease and obesity or overweight, and for a form of fatty liver disease (MASH) with moderate to advanced fibrosis. It now comes as a weekly injection and as a once-daily tablet.7
• Ozempic (semaglutide injection) is approved for adults with type 2 diabetes, including to lower cardiovascular and kidney risks.8
• Rybelsus (oral semaglutide) is a once-daily tablet for adults with type 2 diabetes.9
• Zepbound (tirzepatide) is approved for chronic weight management and for moderate to severe obstructive sleep apnea in adults with obesity.5
• Mounjaro (tirzepatide) is approved for type 2 diabetes in adults and children 10 and older.6

That is why "semaglutide vs Mounjaro" and "tirzepatide vs Ozempic" are really the same question as the one this article answers. For brand-level comparisons, see Ozempic vs Zepbound and Wegovy vs Zepbound, or our explainers on what Ozempic is and what Zepbound is.

On weight loss alone, the trial evidence favours tirzepatide. SURMOUNT-5 randomized 751 adults with obesity but without type 2 diabetes to the maximum tolerated dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg), once weekly for 72 weeks.1

• Average weight change was −20.2% with tirzepatide and −13.7% with semaglutide.1
• In kilograms, that was about 22.8 kg against 15.0 kg.2
• Waist circumference fell by 18.4 cm with tirzepatide and 13.0 cm with semaglutide.1
• People on tirzepatide were more likely to reach weight losses of at least 10%, 15%, 20% and 25%.1

Two caveats belong next to those numbers. The trial was open-label, meaning participants knew which drug they were taking, and it was funded by Eli Lilly, which makes tirzepatide.1 Results in people with type 2 diabetes may also differ, because they were excluded.1

The two drugs' pivotal placebo-controlled trials point the same way. In STEP 1, semaglutide 2.4 mg produced an average change of −14.9% at 68 weeks, against −2.4% with placebo.3 In SURMOUNT-1, tirzepatide produced −15.0%, −19.5% and −20.9% at 5, 10 and 15 mg over 72 weeks, against −3.1% with placebo.4 Comparing separate trials is less reliable than a head-to-head study, which is why SURMOUNT-5 matters.

Averages also hide a wide range. Some people lose far more than the mean and some lose little on either drug, so the better drug for a given person is the one that works and that they can tolerate.

The side-effect profiles are similar: mostly gastrointestinal, mostly mild to moderate, and concentrated during dose increases. That description appears in the SURMOUNT-5, STEP 1 and SURMOUNT-1 papers alike.1,3,4

From the FDA labels' weight-loss trial tables:

• Wegovy 2.4 mg: nausea 44%, diarrhea 30%, vomiting 24%, constipation 24%, against 16%, 16%, 6% and 11% with placebo.7
• Zepbound 15 mg: nausea 28%, diarrhea 23%, vomiting 13%, constipation 11%, against 8%, 8%, 2% and 5% with placebo.5

These figures come from different trials and cannot be compared directly, which the labels themselves note. The head-to-head trial is the fairer test: gastrointestinal events led to stopping treatment in 5.6% of people on semaglutide and 2.7% on tirzepatide.2

Both drugs carry the same boxed warning about thyroid C-cell tumors seen in rodents, and both are contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2.5,7 Both labels also list pancreatitis, gallbladder disease, kidney injury from dehydration, hypoglycemia and aspiration risk under anesthesia among the serious warnings.5,7

Both are injected once a week and started low, then increased every four weeks to limit nausea.

Wegovy injection starts at 0.25 mg weekly for four weeks, then 0.5 mg, 1 mg and 1.7 mg, each for four weeks. From week 17 the usual maintenance dose for weight loss is 2.4 mg, and the label allows up to 7.2 mg for people who have tolerated 2.4 mg for at least four weeks.7

Wegovy tablets start at 1.5 mg once daily for 30 days, then 4 mg and 9 mg, reaching a 25 mg maintenance dose from day 91. They are taken on an empty stomach with up to 4 ounces of water, at least 30 minutes before food or other medicines.7

Zepbound starts at 2.5 mg weekly for four weeks, then rises in 2.5 mg steps at least four weeks apart. Maintenance is 5, 10 or 15 mg, and 15 mg is the maximum.5 The 2.5 mg dose is for starting treatment only.5 For a full schedule, see our Zepbound dosage guide; for doses below the label, see GLP-1 microdosing.

A missed dose is handled differently: Zepbound can be taken within four days of the missed day, and Ozempic within five days.5,8

Self-pay prices from the manufacturers now sit in a similar range. Prices change often, so check the manufacturer's page before relying on them.

• Zepbound via LillyDirect (vial or KwikPen): from $299 a month at 2.5 mg, $399 at 5 mg and $449 at 7.5 mg to 15 mg. The $449 price requires refilling within 45 days; otherwise the regular price is $499 for 7.5 mg and $699 for 10 mg to 15 mg.10
• Wegovy pen via NovoCare Pharmacy: $349 a month for 0.25 mg to 2.4 mg and $399 for Wegovy HD 7.2 mg, with an introductory $199 for the first two fills of 0.25 mg and 0.5 mg through December 31, 2026.11
• Wegovy pill via NovoCare Pharmacy: $149 a month at 1.5 mg, $199 at 4 mg and $299 at 9 mg and 25 mg.11

Insurance coverage varies by plan and by indication. Compounded versions are sometimes advertised at lower prices, but they are not FDA-approved and the FDA does not review their safety, effectiveness or quality before they are sold.12 Our guides to compounded tirzepatide and compounded semaglutide explain where those products stand legally today.

There is no universal winner, but a few factors tend to decide it:

• Size of effect. If the goal is maximum weight loss, tirzepatide has the stronger trial result.1
• Indication. Wegovy has an approved cardiovascular risk-reduction indication; Zepbound has an approved sleep apnea indication.7,5
• Form. Semaglutide is available as a daily tablet for weight loss; tirzepatide is injection-only.7,5 (Supplements sold as "GLP-1 pills" are something else entirely — see do GLP-1 patches work.)
• Tolerability and history. Someone who did well on one drug may stay on it; someone who stalled or struggled may switch, under a clinician's supervision.
• Coverage and cost. What a plan covers, or what the self-pay price is, often decides in practice.10,11

Is tirzepatide stronger than semaglutide? In SURMOUNT-5, average weight loss was 20.2% with tirzepatide and 13.7% with semaglutide at 72 weeks.1 "Stronger" here means more average weight loss, not that every person will respond better.

Is Mounjaro the same as semaglutide? No. Mounjaro contains tirzepatide, a GIP and GLP-1 receptor agonist. Semaglutide is the active ingredient in Ozempic, Wegovy and Rybelsus.6,7

Does tirzepatide have more side effects than semaglutide? The types of side effects are the same, mostly gastrointestinal. In the head-to-head trial, fewer people stopped tirzepatide because of gastrointestinal events (2.7%) than stopped semaglutide (5.6%).2

Can you switch from semaglutide to tirzepatide? Switching is common in practice, but it should be planned with a prescriber, who will choose the starting dose. The labels advise against taking the two together.5

Which is cheaper, Zepbound or Wegovy? It depends on the dose and on insurance. Manufacturer self-pay prices start at $299 a month for Zepbound and $349 a month for the Wegovy pen, with lower introductory or tablet prices for some doses.10,11

If you are weighing the brand-name options side by side, our Wegovy vs Zepbound comparison sets out coverage, price and provider options in one place, and the best GLP-1 providers lists vetted ways to get a prescription.

This article is for information only and is not medical advice. Semaglutide and tirzepatide are prescription drugs with real risks and side effects — talk to a licensed clinician before starting, switching or stopping any treatment.