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Semaglutide vs. tirzepatide: how to choose.
Both are once-weekly injections prescribed through Aryo. Each works in its own way, each has its own price, and both can deliver meaningful results. Here is what the evidence shows.
Published 22 September 2026 · Updated 26 September 2026 · 5 references
The short answer
Tirzepatide acts on two hormone pathways, and in the only head-to-head trial it produced an average weight loss of 20.2% over 72 weeks, compared with 13.7% for semaglutide.5 Semaglutide costs less, plan for plan, and has the longer track record. In the STEP 1 trial, 86% of people taking it lost at least 5% of their body weight.3 Your Aryo clinician recommends the right medication for you at intake.
How they work
Semaglutide mimics GLP-1, a hormone your gut releases after you eat. It signals fullness to your brain, slows how quickly your stomach empties, and helps your body release insulin when blood sugar rises.1 Day to day, that means you feel satisfied on smaller meals, you stay full longer, and food takes up less of your attention.
Tirzepatide works the same way and adds a second hormone, GIP. Acting on both pathways improved blood sugar control beyond what either one achieved alone,2 and it is why tirzepatide produced the larger average weight loss in the head-to-head trial.5
Semaglutide vs. tirzepatide, compared
Semaglutide
The foundation. One hormone pathway, the longer track record.
$139
per month, or $299 for 3 months (about $100/month)
Check eligibilityProgram details
Tirzepatide
Two hormone pathways, and the larger average result in trials.
$199
per month, or $399 for 3 months (about $133/month)
Check eligibilityProgram details| Semaglutide | Tirzepatide |
|---|---|
| Mechanism | |
| Drug class | |
| GLP-1 receptor agonist | Dual GIP and GLP-1 receptor agonist |
| Hormone pathways | |
| One | Two |
| How it is taken | |
| Once-weekly injection | Once-weekly injection |
| Time to therapeutic dose | |
| About 12 to 16 weeks | About 12 to 20 weeks |
| Trial results | |
| Head-to-head resultSURMOUNT-5 · 72 weeks | |
| −13.7%5 | −20.2%5 |
| Weight loss vs. placeboSeparate trials | |
| −14.9% vs. −2.4% placebo68 weeks3 | −20.9% vs. −3.1% placebo72 weeks, 15 mg4 |
| Practical | |
| Aryo price | |
| $139/month$299 for 3 months (about $100/month) | $199/month$399 for 3 months (about $133/month) |
| Known for | |
| Proven results at a lower price | The largest average result in trials |
Figures are mean percentage change in body weight. Numbered markers link to the reference list. Bars are drawn only for the head-to-head trial, where both results come from the same study population.
What the research shows
In the STEP 1 trial, adults with obesity who took semaglutide 2.4 mg for 68 weeks lost an average of 14.9% of their body weight, compared with 2.4% on placebo.3 In SURMOUNT-1, adults who took tirzepatide for 72 weeks lost 15.0%, 19.5% and 20.9% at the 5, 10 and 15 mg doses, compared with 3.1% on placebo.4
Those two trials enrolled different people and ran for different lengths of time, so each result is best read on its own terms.
SURMOUNT-5 compared the two directly. Adults with obesity, without type 2 diabetes, took the highest dose they tolerated of one medication or the other for 72 weeks. Average weight loss was 20.2% on tirzepatide and 13.7% on semaglutide.5
How your clinician chooses
Your clinician weighs your metabolic profile, health history, goals, current medications, and budget, then recommends the program that fits. If your needs change later, you can switch between the two programs on their recommendation.
Program details: Semaglutide · Tirzepatide
Common questions
- In SURMOUNT-5, the only head-to-head trial of the two, people lost an average of 20.2% of their body weight on tirzepatide and 13.7% on semaglutide over 72 weeks. Semaglutide costs less and helps many people reach their goal, so your clinician recommends the one that fits you.
- Semaglutide activates one hormone receptor, GLP-1. Tirzepatide activates two, GLP-1 and GIP. Both are once-weekly injections that reduce appetite and slow gastric emptying, and the second pathway is why tirzepatide produced larger average weight loss in trials.
- Yes. Your Aryo clinician can move you between programs whenever it serves your goals, and guides you through the change.
- Tirzepatide is a newer molecule with a higher acquisition cost for compounding pharmacies. Aryo prices both programs all-inclusive, so the difference reflects the medication itself, with no added fees.
- Aryo's medications are compounded preparations made by state-licensed 503A pharmacies, with the same active ingredient as the brand-name versions. Compounded medications are not FDA-approved and are not reviewed by the FDA for safety, effectiveness, or quality, and they are a separate option from, not a substitute for, the approved branded products.
Is tirzepatide better than semaglutide for weight loss?+
What is the difference between semaglutide and tirzepatide?+
Can I switch from semaglutide to tirzepatide?+
Why does tirzepatide cost more than semaglutide?+
Are Aryo's medications the same as the brand-name versions?+
More in the full FAQ.
References
- 1.Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740-756. doi:10.1016/j.cmet.2018.03.001
- 2.Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab. 2018;18:3-14. doi:10.1016/j.molmet.2018.09.009
- 3.Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183
- 4.Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
- 5.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. doi:10.1056/NEJMoa2416394
Not sure which fits?
Take the eligibility questionnaire. A licensed clinician reviews your history and recommends a program within one business day, with no card required to find out.
Check Eligibility →This page is general health information, not medical advice, and does not replace consultation with a licensed clinician. Semaglutide and tirzepatide are prescription medications. Aryo dispenses compounded preparations through state-licensed 503A pharmacies; compounded medications are not FDA-approved. Trial results cited describe FDA-approved branded products and individual results vary. In clinical trials, treatment was combined with diet and physical activity. Discuss all risks and benefits with your Aryo clinician before starting therapy.