Semaglutide vs tirzepatide for weight loss

Tirzepatide (Zepbound) produced more weight loss on average in its main trial than semaglutide (Wegovy) did in its own. In SURMOUNT-1, people on tirzepatide 15 mg lost 20.9% of their body weight over 72 weeks; in STEP 1, people on semaglutide 2.4 mg lost 14.9% over 68 weeks. When the two were tested against each other in SURMOUNT-5, tirzepatide still came out ahead: 20.2% average weight loss vs 13.7% over 72 weeks.

Semaglutide has its own strengths: a daily pill, a heart-risk indication, a lower full-dose price and a 7.2 mg dose that closed some of the gap. Below are the trial numbers, side effects, dosing and October 2026 prices side by side.

Two ingredients, five brand names

Semaglutide, from Novo Nordisk, acts on the GLP-1 receptor. Tirzepatide, from Eli Lilly, is a dual GIP and GLP-1 receptor agonist: it acts on two hormone receptors instead of one (Zepbound label). Only some of the brands are approved for weight loss.

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Ozempic and Mounjaro have no weight-management indication on their labels. If weight loss is the goal, the brands built for it are Wegovy and Zepbound. Our pages on semaglutide and tirzepatide cover each ingredient in more depth.

Weight loss in the trials

These are the average weight changes from each drug’s headline trials, as printed on the FDA labels. All are intent-to-treat figures, which count everyone assigned to the drug, including people who stopped taking it.

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Zepbound at 10 mg and 15 mg came out 4.6 to 6.0 percentage points ahead of Wegovy 2.4 mg in STEP 1. The 7.2 mg dose, sold as Wegovy HD and approved on March 19, 2026, reached 18.8% in STEP UP, between Zepbound’s 10 mg and 15 mg results. The label allows 7.2 mg only for adults who have tolerated 2.4 mg for at least 4 weeks and need more weight loss.

Those figures come from separate trials with different volunteers. The best evidence on how the two compare is a trial that tested them against each other.

The head-to-head trial: SURMOUNT-5

SURMOUNT-5 randomly assigned 751 adults with obesity but without type 2 diabetes to the highest dose they could tolerate of either tirzepatide (10 mg or 15 mg) or semaglutide (1.7 mg or 2.4 mg), once weekly for 72 weeks. It was published in the New England Journal of Medicine in 2025.

People on tirzepatide were also more likely to reach weight loss of at least 10%, 15%, 20% and 25%. Stomach side effects were the most common in both groups, mostly mild to moderate and mostly while the dose was going up. Two caveats: the trial was open-label, so participants knew which drug they were taking, and it was funded by Eli Lilly, which makes tirzepatide.

A diabetes comparison on the Mounjaro label

The Mounjaro label includes SURPASS-2, a 40-week trial in adults with type 2 diabetes that compared tirzepatide with semaglutide 1 mg. Body weight fell 7.6 kg, 9.3 kg and 11.2 kg on tirzepatide 5, 10 and 15 mg, against 5.7 kg on semaglutide. Semaglutide 1 mg is an Ozempic dose, well below Wegovy’s 2.4 mg, so this trial matters most for people with diabetes.

Side effects

Stomach side effects are the most common on both drugs. These are the rates from the label tables:

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Zepbound’s rates look lower, but so do its placebo rates, and the numbers come from different trials. Compare each drug with its own placebo column. For the Wegovy pill, the label says common side effects were similar to the injection’s, and 6.9% stopped because of side effects against 5.9% on placebo.

Both labels carry a boxed warning for thyroid C-cell tumors, and neither drug is for anyone with a personal or family history of medullary thyroid carcinoma or MEN 2. Our side effects guide covers the rest.

How you take each one

The Wegovy injection is weekly. It starts at 0.25 mg for weeks 1 to 4, steps up every 4 weeks through 0.5, 1 and 1.7 mg, and reaches a maintenance dose of 2.4 mg (or 1.7 mg) from week 17.

The Wegovy pill is daily, taken in the morning on an empty stomach with up to 4 oz of water, then at least 30 minutes before food, drink or other oral medicines. It goes from 1.5 mg to 4 mg to 9 mg, 30 days each, then 25 mg from day 91.

Zepbound is weekly. It starts at 2.5 mg for 4 weeks, then 5 mg, and can rise in 2.5 mg steps at least 4 weeks apart to a maintenance dose of 5, 10 or 15 mg. Your prescriber sets the pace.

Approved uses beyond weight loss

• Wegovy (injection and pill) is approved to lower the risk of cardiovascular death, heart attack and stroke in adults with established cardiovascular disease and obesity or overweight, a use the FDA first approved on March 8, 2024. The injection also has an accelerated approval for MASH, a liver disease, with moderate to advanced fibrosis.
• Zepbound is approved for moderate to severe obstructive sleep apnea in adults with obesity, since December 20, 2024.

These uses can change how insurance handles the drug. Medicare’s $50 GLP-1 Bridge, for example, sends them to your regular Part D plan, as our Medicare guide explains.

What each costs in October 2026

Monthly Wegovy prices are from NovoCare Pharmacy and Zepbound prices from LillyDirect, both read October 17, 2026. A Zepbound refill at 7.5 mg or higher outside the 45-day window costs $499 (7.5 mg) or $699 (10 to 15 mg). With commercial insurance that covers the drug, both makers’ savings offers can cut the cost to as little as $25 a month, though people with government insurance can’t use them.

Compounded versions cost less at many online programs: taking each program’s lowest ongoing monthly price at the 39 programs we rank, as of October 2026, compounded semaglutide runs $89 to $299 a month and compounded tirzepatide $125 to $399. altRx, for example, lists $89 a month for semaglutide and $149 for tirzepatide at every dose. Compounded versions are not Wegovy, Ozempic, Zepbound or Mounjaro, and not generics of them. A compounding pharmacy prepares them, and they are not FDA-approved or reviewed by the FDA for safety, effectiveness or quality. See our compounded semaglutide rankings before you choose one.

Which one fits you

• For the largest average loss seen in trials, Zepbound 10 mg and 15 mg posted the highest numbers, in trials separate from Wegovy’s.
• If you’d rather not inject, the Wegovy pill is daily semaglutide. Foundayo is another daily pill with a different active ingredient; see Foundayo vs the Wegovy pill.
• With established heart disease, Wegovy is the one with a heart-risk indication.
• With obstructive sleep apnea and obesity, Zepbound is the one approved for it.
• On cost alone, the Wegovy pill ($299) and injection ($349) are cheaper at full dose than Zepbound ($449 with on-time refills).

A licensed clinician can weigh these against your health history, other medicines and coverage. Run your own numbers in our GLP-1 cost calculator, then use our match tool to find programs that prescribe the drug you pick.

The bottom line

Tirzepatide posted bigger average weight loss than semaglutide in their separate main trials: 20.9% at 15 mg over 72 weeks in SURMOUNT-1, against 14.9% at 2.4 mg over 68 weeks in STEP 1. It also led semaglutide 1 mg in SURPASS-2, a diabetes trial. Semaglutide offers a pill, a heart-risk indication, a 7.2 mg dose that reached 18.8% in STEP UP and a lower full-dose cash price.

Neither drug guarantees a result. Talk the options through with a licensed clinician before you choose.