Semaglutide
- Class
- GLP-1 receptor agonist
- Form
- Once a week, injection
- Dose steps
- 0.25 mg, then 0.5, 1.0, 1.7, and 2.4 mg, increasing every 4 weeks
- vs. placebo
- 14.9% vs. 2.4% at 68 weeks (STEP 1, 2.4 mg)
- Head to head
- 13.7% at 72 weeks (SURMOUNT-5)
Semaglutide vs. tirzepatide
Semaglutide and tirzepatide are both once-weekly injections for weight management. Semaglutide acts on one gut hormone receptor (GLP-1), and tirzepatide acts on two (GIP and GLP-1). In the one large head-to-head trial, people on tirzepatide lost more weight on average, but both have similar side effects, and a clinician decides which, if either, suits you.
Trial results come from the FDA-approved brand-name drugs, not compounded versions. Averages describe groups, and your results may differ.
Start your online visitSide by side
You choose semaglutide or tirzepatide. Semaglutide is from $79/mo when prescribed. Tirzepatide is from $89/mo when prescribed. Online visit.
Tirzepatide
from$89/mo
when prescribed (compounded)
Dual GIP and GLP-1 receptor agonist, once a week. 2.5 mg, then up 2.5 mg every 4 weeks, to 5, 10, or 15 mg. 15.0%, 19.5%, 20.9% vs. 3.1% at 72 weeks (SURMOUNT-1, 5/10/15 mg). 20.2% at 72 weeks in SURMOUNT-5.
Start your online visitThe full comparison
Trial results come from the FDA-approved brand-name drugs, not compounded versions.
| Semaglutide | Tirzepatide | |
|---|---|---|
| How it works | GLP-1 receptor agonist | Dual GIP and GLP-1 receptor agonist |
| How often | Once a week, injection | Once a week, injection |
| Dose steps in trials | 0.25 mg, then 0.5, 1.0, 1.7, and 2.4 mg, increasing every 4 weeks | 2.5 mg, then up 2.5 mg every 4 weeks, to 5, 10, or 15 mg |
| Average weight loss vs. placebo | 14.9% vs. 2.4% at 68 weeks (STEP 1, 2.4 mg) | 15.0%, 19.5%, 20.9% vs. 3.1% at 72 weeks (SURMOUNT-1, 5/10/15 mg) |
| Head to head (SURMOUNT-5) | 13.7% at 72 weeks | 20.2% at 72 weeks |
| Common side effects | Nausea, diarrhea, vomiting, constipation, stomach pain | Nausea, diarrhea, vomiting, constipation, stomach pain |
| Rxely price | From $79/mo | From $89/mo |
Averages describe groups, and your results may differ. Check your BMI
How each one works
Both medications copy hormones your gut releases after you eat. Semaglutide activates the GLP-1 receptor, which slows stomach emptying and signals fullness to the brain. Tirzepatide activates the GLP-1 receptor and the GIP receptor, a second hormone pathway involved in appetite and blood sugar.
Dosing and titration
Each is a weekly injection under the skin. Both start at a low dose and go up in steps about every four weeks, which helps your body adjust. In the trials, semaglutide moved from 0.25 mg toward 2.4 mg over 16 weeks, and tirzepatide started at 2.5 mg and rose by 2.5 mg steps. Your clinician sets your own schedule and may hold or lower a dose based on how you feel. Every tirzepatide step is laid out in the tirzepatide dosing chart. Ours is compounded tirzepatide, from $89 a month.
What the trials found
- STEP 1 (Wilding et al., NEJM 2021): adults without diabetes on semaglutide 2.4 mg lost 14.9% of body weight on average at 68 weeks, compared with 2.4% on placebo.
- SURMOUNT-1 (Jastreboff et al., NEJM 2022): adults without diabetes on tirzepatide lost 15.0%, 19.5%, and 20.9% on average at 5, 10, and 15 mg over 72 weeks, compared with 3.1% on placebo.
- SURMOUNT-5 (Aronne et al., NEJM 2025): in a direct comparison at the highest tolerated doses, average weight loss at 72 weeks was 20.2% with tirzepatide and 13.7% with semaglutide.
All three trials paired medication with diet and activity counseling and studied the brand-name drugs, not compounded versions.
Side effects and safety
The most common side effects for both are nausea, diarrhea, vomiting, and constipation. In the trials, most were mild to moderate and showed up while the dose was increasing.
Boxed warning
Both carry a boxed warning about thyroid C-cell tumors seen in rodent studies. They are not for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Other serious risks include pancreatitis and gallbladder problems. Talk with a clinician about your history before starting either one.
Who might lean which way
Some people lean toward semaglutide because it has been in use longer and starts at a lower price. Others lean toward tirzepatide because of the larger average weight loss in SURMOUNT-5. You choose which one to request. A licensed clinician reviews your health history and decides whether to prescribe it.
Not sure you're in range? Use our BMI calculator first, or start your online visit.
Sources
- Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989-1002. doi:10.1056/NEJMoa2032183
- Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-216. doi:10.1056/NEJMoa2206038
- Aronne LJ, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025. doi:10.1056/NEJMoa2416394
- Trial dose schedules: NCT03548935 (STEP 1), NCT05822830 (SURMOUNT-5)
Questions
Which works better, semaglutide or tirzepatide?
In SURMOUNT-5, a 72-week head-to-head trial of the brand-name drugs, people on tirzepatide lost 20.2% of body weight on average, compared with 13.7% on semaglutide. Results vary from person to person, and the trial did not study compounded versions.
Are both taken as a weekly shot?
Yes. Both are injected under the skin once a week. The dose starts low and goes up in steps about every four weeks.
Which has fewer side effects?
Both have similar side effects. The most common are nausea, diarrhea, vomiting, and constipation, mostly mild to moderate and most frequent while the dose is going up. Your clinician can help you weigh this against your history.
Can I pick which one I get?
Yes, you choose semaglutide or tirzepatide in your assessment. A licensed clinician then reviews your health history and decides whether to prescribe it.
How much do they cost at Rxely?
Compounded semaglutide plans start at $79/mo and compounded tirzepatide plans start at $89/mo. You pay for medication only if a clinician prescribes it.
Are compounded versions the same as the brand-name drugs?
No. Compounded medications are prepared by a licensed pharmacy and are not FDA-approved. They are not the same as Ozempic, Wegovy, Mounjaro, or Zepbound, and the trials on this page studied the brand-name drugs.
Who are your pharmacies?
Prescriptions are filled by two licensed pharmacies: Rush Pharmacy and Epiq Scripts.
Who is your provider network?
Care is provided by licensed clinicians through LocumTele, an independent network of licensed clinicians.
Do you serve all 50 states?
Yes. Rxely is available in all 50 states. Eligibility is decided by a licensed clinician after your assessment, and a prescription is not guaranteed.
How long does shipping take?
If prescribed, cold-pack medications ship next-day. Non-sterile medications ship by ground. Each order comes with written instructions.
What is your refund policy?
We don't offer refunds on medication. We replace it instead.