Semaglutide vs tirzepatide: which works better, side effects and cost

Tirzepatide produced more weight loss than semaglutide in the only head-to-head trial, by about 6.5 percentage points at 72 weeks. That does not make it the right drug for everyone. Semaglutide (Wegovy, Ozempic, Rybelsus) acts on one gut-hormone receptor, GLP-1, and comes as a pill. Tirzepatide (Zepbound, Mounjaro) acts on two, GIP and GLP-1, and comes only as an injection. Everything beyond that single trial is a comparison across separate studies, flagged as such.

SURMOUNT-5: the only head-to-head weight trial

SURMOUNT-5 randomized 751 adults with obesity and no type 2 diabetes to the highest dose each person tolerated: tirzepatide 10 or 15 mg, or semaglutide 1.7 or 2.4 mg, injected weekly for 72 weeks. Everyone also followed a lifestyle program. The trial was open-label (participants knew which drug they got) and was funded by Eli Lilly, the maker of tirzepatide.

The headline percentages come from the NEJM paper. The shares reaching each threshold are as posted in the trial’s ClinicalTrials.gov results, and the kilogram figures come from the American College of Cardiology’s summary. Comparing only the top doses, 15 mg against 2.4 mg, the registry reports 21.8% versus 15.4%.

Read the threshold rows, because they show what the averages hide. Nearly a third of people on semaglutide lost 20% or more, and about 1 in 8 on tirzepatide did not reach 10%.

Who might each drug suit?

The prescriber makes this call, and your insurance often does too. Here is where the evidence and labels point.

Tirzepatide tends to come up when the main goal is the most weight loss, or when obstructive sleep apnea is part of the picture, since Zepbound is labeled for it. In the head-to-head trial it also had the lower rate of stopping for stomach side effects.

Semaglutide tends to come up in four situations:

• You want a pill. The Wegovy tablet has no tirzepatide equivalent.
• You have heart disease and excess weight, without diabetes. Wegovy has a labeled heart-risk use based on the SELECT trial. Mounjaro’s heart-risk use applies only with type 2 diabetes, and Zepbound has none.
• You have MASH with moderate to advanced scarring. The Wegovy injection has an accelerated approval for it.
• You are not reaching your goal on 2.4 mg. Wegovy HD (7.2 mg) gives a further labeled step, though its skin-sensation side effect needs weighing.

If you have type 2 diabetes, the brands change to Ozempic or Rybelsus, and Mounjaro, and both drugs have a labeled heart-risk use. A daily pill and a weekly shot also ask different things of your routine.

What the comparison cannot tell you

SURMOUNT-5 settles less than the headlines suggest, for a few reasons:

• It stopped at 2.4 mg. Semaglutide 7.2 mg (Wegovy HD), approved in March 2026, was not tested against tirzepatide.
• It excluded people with type 2 diabetes. It says nothing direct about weight loss in that group.
• It did not test pills. There is no head-to-head trial of the Wegovy pill against tirzepatide.
• It did not measure heart outcomes. It was a weight trial, so it cannot say which drug better prevents heart attacks or strokes.
• It was open-label and funded by Lilly. People knew which drug they were on.

It also says nothing about you in particular. An average gap of 6.5 points sits on top of a wide spread in both groups, and how you respond to one drug is something only treatment can show. We found no new head-to-head randomized trial of the two in 2026.

Other comparisons, with caveats

These numbers come from separate trials with different people, lengths and methods. Treat any gap as a rough signal, never a ranking.

Blood sugar in type 2 diabetes

In type 2 diabetes, the SURPASS-2 trial did compare the two directly, with semaglutide at the Ozempic dose of 1 mg. Over 40 weeks, A1c (a 3-month blood sugar average) fell by 2.01, 2.24 and 2.30 points on tirzepatide 5, 10 and 15 mg, against 1.86 points on semaglutide 1 mg. Ozempic now goes up to 2 mg, a dose SURPASS-2 did not test.

Which is better for the heart?

No trial has compared the two head to head on heart attacks and strokes. Each drug now has a heart-risk use on a label, but they cover different people and rest on different kinds of trial.

Do not line those two columns up as a contest. SELECT measured a drug against no active treatment, and SURPASS-CVOT measured one against another effective drug, so the percentages say different things. SURPASS-CVOT was funded by Lilly.

If your interest is weight loss without diabetes, the practical point is simpler. Zepbound, the tirzepatide brand for weight, has no heart-risk use on its label, and Mounjaro’s use requires type 2 diabetes. With diabetes, semaglutide has labeled heart-risk uses too: Ozempic for adults with established heart disease, and the tablets for adults at high risk.

The best indirect evidence in diabetes is a study of US insurance records, funded by the National Institutes of Health and the German Heart Foundation. After matching 172,382 adults with obesity and type 2 diabetes who started one drug or the other, the 1-year risk of death, heart attack or stroke was 1.3% on each (hazard ratio 1.06, 95% CI 0.95 to 1.18). The authors read that as compatible with no difference. An observational study like this cannot rule out differences between the people who got each drug.

Dosing ladders

The Wegovy pill climbs every 30 days from 1.5 mg to 4, 9 and 25 mg daily. Full tables, pen strengths and unit conversions are on the semaglutide dosage chart and the tirzepatide dosage chart.

Side effects compared

The stomach side effects in SURMOUNT-5 were close, with a few differences. These figures come from the trial’s posted results:

Stopping treatment because of stomach side effects was 5.6% on semaglutide versus 2.7% on tirzepatide.

The labels, drawn from each drug’s own placebo-controlled trials, tell a similar story. On Wegovy 2.4 mg, nausea affected 44% versus 16% on placebo, and 6.8% stopped because of side effects versus 3.2%. On Zepbound, nausea affected 25% to 29% across doses versus 8%, and 4.8% to 6.7% stopped versus 3.4%. Those numbers come from different trials, so do not read the gap in nausea as a direct comparison. SURMOUNT-5 is the better guide.

One side effect is specific to semaglutide’s top dose. Dysesthesia, an altered or burning skin sensation, affected 22% of people on Wegovy HD 7.2 mg versus 6% on 2.4 mg.

Both drugs carry the same boxed warning about thyroid C-cell tumors in rodents, and the same serious warnings for pancreatitis, gallbladder disease, kidney injury from dehydration, low blood sugar with insulin or a sulfonylurea, diabetic eye complications and aspiration under anesthesia. Both labels removed their suicidal ideation warning in early 2026. The semaglutide side effects and tirzepatide side effects guides have the full label tables.

Forms: pens, vials and pills

Semaglutide. Wegovy comes as single-dose pens from 0.25 mg to 7.2 mg, single-dose prefilled syringes, and a multi-dose FlexTouch pen holding four 2.4 mg doses. Ozempic comes in multi-dose pens and single-dose prefilled syringes. Semaglutide is the only one of the two with pills: Wegovy tablets for weight, and Ozempic tablets and Rybelsus for type 2 diabetes. The pills go on an empty stomach with no more than 4 ounces of water, at least 30 minutes before food, drinks or other oral medicines.

Tirzepatide. Zepbound comes as single-dose pens, single-dose vials (sold only through Lilly’s self-pay pharmacy) and a multi-dose KwikPen holding four weekly doses. There is no tirzepatide pill.

Which is cheaper, Wegovy or Zepbound?

At maintenance doses, Wegovy costs less: $299 to $399 a month against $399 to $449 for Zepbound with on-time refills. List prices are rarely what anyone pays: Wegovy lists at about $1,349 a month, and Lilly listed Zepbound at up to $1,086.37 as of January 1, 2026. Novo says Wegovy’s list price falls to $675 on January 1, 2027, with no effect on self-pay prices. The self-pay programs, checked November 2, 2026:

At the labeled maintenance doses, then, the Wegovy pill is $299, the Wegovy pen $349 and Zepbound 5 mg $399, with Zepbound 10 or 15 mg at $449 if you refill on time. Novo also sells 3-, 6- and 12-month Wegovy subscriptions through some telehealth providers, with pens from $249 a month on the 12-month plan.

With commercial insurance that covers the drug, both companies offer savings cards that can bring the cost to as little as $25 a month; government beneficiaries are excluded. Either company can change these programs at any time. The cheapest GLP-1 without insurance guide compares every route.

Can you switch, or take both?

You should not take both. The Wegovy label says it is not recommended with any other GLP-1 drug, and Zepbound’s information says it should not be used with any GLP-1 medicine. Neither label sets a dose conversion between them, so switching is a plan to work out with a prescriber. On stepping down a dose, tirzepatide has SURMOUNT-MAINTAIN, in which people who had lost weight and moved to 5 mg kept off less than those who stayed on their highest tolerated dose: 16.6% below their starting weight versus 21.9%, and 9.9% on placebo, at week 112.

Who should not use either

The contraindications match: a personal or family history of medullary thyroid carcinoma, Multiple Endocrine Neoplasia syndrome type 2, or a prior serious allergic reaction to the drug. Pregnancy plans matter too, and the Wegovy label advises stopping at least 2 months before a planned pregnancy. Which drug fits depends on your health history, your insurance, whether you want a pill and how you tolerate the first weeks. For new approvals that change this comparison, see the FDA status tracker.