Published August 27, 2026 · updated August 27, 2026 · regulatory and clinical facts last checked 2026-08-27 · medically reviewed by Dr. S. Shuwart, MD on August 27, 2026

Medically reviewed · August 27, 2026

Tirzepatide vs semaglutide: the head-to-head evidence

What the direct comparison trial and the indirect comparisons show about weight change, tolerability, and where the two medications differ in cost and availability through telehealth.

The direct comparison

SURMOUNT-5 randomised adults with obesity and without diabetes to tirzepatide (titrated to the maximum tolerated dose, up to 15 mg weekly) or semaglutide 2.4 mg weekly for 72 weeks. Mean weight change was about −20.2% on tirzepatide and about −13.7% on semaglutide. The trial was open label, which is a limitation, and it compared the maximum tolerated tirzepatide dose with semaglutide’s single approved maintenance dose.

In type 2 diabetes, SURPASS-2 compared tirzepatide 5, 10 and 15 mg with semaglutide 1 mg (the dose then approved for diabetes) over 40 weeks and found greater glucose lowering and weight reduction with tirzepatide at every dose.

The indirect comparison

The placebo-controlled trials in similar populations point the same way: about −21% at tirzepatide 15 mg over 72 weeks in SURMOUNT-1 versus about −15% at semaglutide 2.4 mg over 68 weeks in STEP 1. Indirect comparisons across trials with different designs are weaker evidence than a head-to-head trial, but here they agree with it.

Tolerability

Both medications share the gastrointestinal adverse-event profile of the class, concentrated during dose escalation, and similar label warnings. Discontinuation rates for adverse events were broadly similar in the head-to-head trial. Individual tolerability varies and is one reason some patients do better on one than the other.

Beyond weight

Semaglutide has a cardiovascular outcomes trial in people with obesity and established cardiovascular disease (SELECT), and a corresponding indication. Tirzepatide has the obstructive sleep apnoea indication and outcomes trials in progress at the time of our last review. Which of these matters depends on the individual’s history and is a clinical decision.

Cost and availability through telehealth

On this site the two medications are priced from the same records by the same method. At our latest verification the lowest verified compounded prices are $104–$130 per month for tirzepatide and $95 per month for semaglutide, both at the starting dose and both before a consultation fee the provider does not publish; brand-name pathways cost several times more. The tirzepatide and semaglutide pricing pages show every verified plan, and the maintenance-dose calculator shows what each costs at the dose you may reach. The choice of medication is clinical; the price comparison is only useful once that choice is made with a clinician.

Sources

Aronne LJ et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med 2025 (trial)
Frías JP et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). N Engl J Med 2021 (trial)
Jastreboff AM et al. SURMOUNT-1. N Engl J Med 2022 (trial)
Wilding JPH et al. STEP 1. N Engl J Med 2021 (trial)
Verified tirzepatide and semaglutide plan prices in the pricing database (provider)

Educational information, not medical advice. Decisions about GLP-1 medication belong with you and a licensed clinician who knows your history. Compounded medications are not FDA-approved. Report an error.