Tirzepatide vs. semaglutide: how they compare for weight loss
Both are GLP-1 medications used for weight loss, and one head-to-head trial has compared them directly. Here is what that trial reported, what both labels say about side effects, and how Temi prices each.
Medically reviewed by Kevin Brandstetter, M.D.Last reviewed September 4, 2026
- Head-to-head trial data
- Not medical advice
The basic difference
Tirzepatide (the active ingredient in Zepbound and Mounjaro) is a dual GIP/GLP-1 receptor agonist: it acts on two gut-hormone pathways. Semaglutide (the active ingredient in Wegovy and Ozempic) acts on GLP-1 alone. Both reduce appetite and slow digestion; the added GIP pathway is the mechanistic difference the head-to-head trial set out to test.
What the head-to-head trial found
SURMOUNT-5 was a 72-week, randomized, open-label Phase 3b trial. It randomized 751 adults with obesity and without diabetes to the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or of semaglutide (1.7 mg or 2.4 mg), injected once weekly.1
-20.2%
Average weight change at week 72 on tirzepatide1
-13.7%
Average weight change at week 72 on semaglutide1
Waist circumference fell 18.4 cm with tirzepatide and 13.0 cm with semaglutide, and participants taking tirzepatide were more likely than those taking semaglutide to reach weight reductions of at least 10%, 15%, 20%, and 25%.1 These are averages at maximum tolerated doses in one trial population. Individual results vary, and your clinician will weigh your health history before recommending either medication.
Side effects
In SURMOUNT-5, the most common adverse events in both treatment groups were gastrointestinal; most were mild to moderate and occurred mainly while the dose was being increased.1 Both products' FDA-approved prescribing information lists nausea, diarrhea, vomiting, constipation, and abdominal pain among the adverse reactions reported in at least 5% of patients.23 Each label carries further warnings, and your prescribing clinician reviews your full health history and current medications to assess your individual risk.
Pricing at Temi
| Option | Starting price at Temi |
|---|---|
| Compounded semaglutide injectable | From $74.99 per fill + $39 service4 |
| Compounded tirzepatide injectable | From $109.99 per fill + $39 service4 |
A fill is one vial, which is used for 28 days after it is opened rather than a calendar month. The $39 prescription service is what a non-member pays per order; Temi Care includes it. Each starting price above is one a patient can reach in every state Temi serves; some states start lower. Your own price depends on your dose, your pharmacy, and your state, and Temi shows it in full before you are charged.
Temi does not sell or dispense the brand-name products. For reference, Eli Lilly's published self-pay price for Zepbound through LillyDirect starts at $299 per month.5 A compounded preparation is not an equivalent of the commercially available product.
Which one is right for you?
This is not a decision to make from a trial average alone. A Temi clinician weighs your health history, other medications, prior GLP-1 experience, tolerability, and goals, the same questions any prescriber should ask before recommending either drug over the other.
Frequently asked questions
- Is tirzepatide always more effective than semaglutide?
- In the SURMOUNT-5 head-to-head trial, tirzepatide produced greater average weight loss than semaglutide at maximum tolerated doses over 72 weeks. That is a trial average, not a prediction for one person. Individual response varies, and some patients do better on one medication than the other.
- Can I switch from semaglutide to tirzepatide?
- Some patients do, under clinician guidance. Your prescribing physician determines an appropriate transition plan based on your current dose, your response, and your health history.
- Is compounded tirzepatide or semaglutide FDA-approved?
- No. Compounded versions of both are not FDA-approved. The FDA-approved brand versions are Zepbound and Mounjaro for tirzepatide, and Wegovy and Ozempic for semaglutide.
Sources
- Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025;393(1):26-36. SURMOUNT-5, ClinicalTrials.gov NCT05822830. doi:10.1056/NEJMoa2416394
- ZEPBOUND (tirzepatide) injection, FDA-approved prescribing information, Eli Lilly and Company, section 6.1. DailyMed
- WEGOVY (semaglutide) injection, FDA-approved prescribing information, Novo Nordisk, section 6.1. DailyMed
- Temi pricing: read at build time from Temi's own pharmacy catalog, the same projection the medication pages and the GLP-1 cost calculator price from.
- Zepbound self-pay price: Eli Lilly's published LillyDirect pricing, maintained in Temi's catalog as the branded comparison.
Medically reviewed content. This page describes prescription medications, including compounded preparations that are not FDA-approved. It is not medical advice; individual results and eligibility vary, so consult a licensed clinician.
Compounded semaglutide and compounded tirzepatide are not FDA-approved generics of the brand-name products. A licensed 503A compounding pharmacy prepares each one for a single prescription.
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