Comparison
Tirzepatide vs. semaglutide for weight loss: what's the difference?
By the TreatmentMD editorial team
Medically reviewed by Christopher Stephenson, MD
Key takeaways
- In the one study that compared them directly, people taking tirzepatide lost more weight on average than those taking semaglutide: about 20% of their body weight versus about 14%.1The New England Journal of MedicineRandomized trial · 2025SURMOUNT-5People lost 20.2% of their weight on tirzepatide and 13.7% on semaglutide, in the only trial to compare the two directly.751 people · 72 weeks. Adults with obesity, without diabetes. Open label, funded by Eli Lilly.Tirzepatide as compared with semaglutide for the treatment of obesity. Aronne LJ, et al., 2025.Read the study All sources Individual results vary.
- Both curb appetite by copying gut hormones. Tirzepatide acts on two hormones; semaglutide acts on one.
- Both are medicines for medical weight loss or diabetes that require a prescription. Tirzepatide is a weekly shot; semaglutide comes as a weekly shot or, for some products, a daily pill.
By the TreatmentMD editorial team
If you're comparing weight-loss medication, two names come up again and again: tirzepatide (sold as Zepbound®) and semaglutide (sold as Wegovy®).
They're closely related, but they're not the same, and the right choice depends on you.
Here's how they compare in terms of how they work, results, side effects, and cost.
01At a glance
Tirzepatide vs. semaglutide at a glance
| Tirzepatide (Zepbound®) | Semaglutide (Wegovy®) | |
|---|---|---|
| How it works | Copies two gut hormones (GLP-1 and GIP) to curb appetite | Copies one gut hormone (GLP-1) to curb appetite |
| Approved for weight loss | Yes, as Zepbound®. (Mounjaro® is the same drug but approved for type 2 diabetes.)2U.S. Food and Drug AdministrationSourceFDA prescribing information for Zepbound®, Wegovy®, Mounjaro®, and Ozempic®: Indications and Usage; Boxed Warning; Contraindications; Warnings and Precautions.All sources | Yes, as Wegovy®. (Ozempic® is the same drug but approved for type 2 diabetes.)2U.S. Food and Drug AdministrationSourceFDA prescribing information for Zepbound®, Wegovy®, Mounjaro®, and Ozempic®: Indications and Usage; Boxed Warning; Contraindications; Warnings and Precautions.All sources |
| How you take it | Weekly injection | Weekly injection, or a daily pill for some products |
| Common side effects | Nausea, diarrhea, constipation, belly pain, fatigue | Similar, plus headache and dizziness |
| Cost without insurance | Historically around $1,000/month; self-pay programs can lower this. Compounded medications may cost under $250 per month. | Historically around $1,000/month; self-pay programs can lower this. Compounded medications may cost under $150 per month. |
02How they work
How they work
Both medicines copy hormones your gut releases after you eat. These hormones tell your brain you're full and slow how fast your stomach empties, so you feel satisfied longer and tend to eat less.
The main difference is how many hormones each one copies. Semaglutide acts like one hormone (GLP-1). Tirzepatide acts like two (GLP-1 and a second one called GIP).
Working on two pathways may be part of why tirzepatide tends to lead to a bit more weight loss.
03Results
How well do they work?
Both lead to significant weight loss for many people.
When researchers compared them head-to-head, people on tirzepatide lost more on average: about 20% of their body weight, versus about 14% on semaglutide, over roughly 72 weeks.1The New England Journal of MedicineRandomized trial · 2025SURMOUNT-5People lost 20.2% of their weight on tirzepatide and 13.7% on semaglutide, in the only trial to compare the two directly.751 people · 72 weeks. Adults with obesity, without diabetes. Open label, funded by Eli Lilly.Tirzepatide as compared with semaglutide for the treatment of obesity. Aronne LJ, et al., 2025.Read the study All sources
That's a real difference, but it's an average: some people respond better to one than the other.
Your results depend on your body, your dose, how well you tolerate the medicine, and staying on it alongside healthy eating and activity.
04Safety
Side effects and safety
The most common side effects are similar for both medicines and often ease over time, especially after the first few weeks or after a dose increase:
05Cost
Cost and access
Without insurance, brand-name versions have been expensive (historically around $1,000 a month), though manufacturer self-pay programs have brought starting costs down for many people.
Insurance coverage varies, and plans often don't cover a medicine used only for weight loss.
Some telehealth providers offer lower-cost compounded versions prepared for an individual patient (more on those in the FAQ).
Coverage is also changing for Medicare patients: starting in July 2026, Medicare began covering some GLP-1 medicines for weight loss through a temporary program, with copays capped at $50 a month through the end of 2027 for people who qualify.3Centers for Medicare and Medicaid ServicesSourceCMS. Medicare GLP-1 Bridge program (July 1, 2026 through December 31, 2027; $50 monthly copay for eligible beneficiaries).Open the source All sources
Manufacturer savings cards can help, too.
06Choosing
Which one is right for you?
There's no single best choice for everyone. A few things to consider:
Your goals
If the most weight loss on average is the priority, tirzepatide has the edge in head-to-head research.
What you've tried
If you've done well on semaglutide, or you'd prefer a pill, that matters.
Branded vs. compounded
Brand-name products are FDA-approved and backed by vetted research but cost more. Compounded versions are usually more affordable but aren't FDA-approved.
Cost and access
Your insurance, savings programs, and the provider you choose all affect what you'll pay and how easily you can stay on treatment.
A licensed provider can help you decide which option is best for your unique needs.
Frequently asked questions.
Which costs less, tirzepatide or semaglutide?
While semaglutide is usually priced lower than tirzepatide, cost depends on a variety of factors.
Brand-name versions of both can run around $1,000 a month without insurance, though manufacturer self-pay programs and savings cards can lower that.
What you actually pay depends more on your insurance, pharmacy, and dosage.
Check coverage for both before you decide.
What are compounded GLP-1 medications?
Compounded semaglutide and tirzepatide are custom-made versions prepared by state-licensed pharmacies, often at a lower cost.
They are not FDA-approved, so the FDA doesn't check their safety, quality, or effectiveness, and the trial results for the brand-name drugs don't carry over to them.
Wide access to compounded versions was tied to national shortages; after the FDA declared those resolved in late 2024 and early 2025, compounding is generally allowed when a licensed provider documents a specific medical reason a standard product won't meet for an individual patient.4U.S. Food and Drug AdministrationSourceFDA. Clarification of compounding policies as national GLP-1 supply stabilizes (shortage resolutions and 503A pathway).Open the source All sources
That's why the pharmacy behind a prescription matters, and it's one of the things we weigh when comparing providers.
Can I switch from semaglutide to tirzepatide?
Many people do, often to get more weight loss or because of side effects or cost.
However, it should be a decision you make with your provider, not on your own.
The bottom line
Tirzepatide and semaglutide both work well, and in head-to-head research, tirzepatide led to more weight loss on average.
Side effects, cost, and how you respond all matter, so the best fit is personal.
Compare options on our Best Weight Loss Medications list and always speak with a licensed provider to determine next steps for your weight loss journey.
By the TreatmentMD editorial team
Medical disclaimerThis content is for informational purposes only and is not medical advice. Always consult a qualified healthcare provider before starting any weight-loss program or medication. Individual results may vary.
Sources
- 1Aronne LJ, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (head-to-head trial). N Engl J Med. 2025;393(1):26-36. DOI: 10.1056/NEJMoa2416394 doi.org
- 2FDA prescribing information for Zepbound®, Wegovy®, Mounjaro®, and Ozempic®: Indications and Usage; Boxed Warning; Contraindications; Warnings and Precautions.
- 3CMS. Medicare GLP-1 Bridge program (July 1, 2026 through December 31, 2027; $50 monthly copay for eligible beneficiaries). cms.gov
- 4FDA. Clarification of compounding policies as national GLP-1 supply stabilizes (shortage resolutions and 503A pathway). fda.gov
Product information
- Zepbound® (tirzepatide) is a prescription-only injectable medication FDA-approved for chronic weight management in adults with obesity, or adults with overweight who have at least one weight-related medical condition. It is also approved for the treatment of moderate to severe obstructive sleep apnea in adults with obesity, and should be used in combination with a reduced-calorie diet and increased physical activity.
- Ozempic® (semaglutide) is a prescription-only injectable medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes. It is not FDA-approved for weight loss; however, weight reduction has been observed in some individuals with type 2 diabetes using the medication.
- Mounjaro® (tirzepatide) is a prescription-only injectable medication FDA-approved for the treatment of type 2 diabetes. It is not FDA-approved for weight loss; however, weight reduction has been observed in some individuals using the medication.
- Wegovy® (semaglutide) is a prescription-only injectable medication FDA-approved for chronic weight management in adults with obesity, or adults with at least one weight-related medical condition, when used alongside a reduced-calorie diet and increased physical activity.
- All medications require a medical evaluation and prescription from a licensed healthcare provider. Individual results may vary.
Important safety information
- Compounded semaglutide and tirzepatide are prepared by state-licensed pharmacies and are not FDA approved. The FDA does not review their safety, effectiveness or quality, and clinical trial results for brand-name drugs do not carry over to them.
- Semaglutide and tirzepatide carry a boxed warning for a risk of thyroid C-cell tumors, based on animal studies, and are not for anyone with a personal or family history of medullary thyroid carcinoma (MTC) or MEN2, or who is pregnant. Other warnings include pancreatitis, gallbladder problems, and a higher risk of low blood sugar when combined with insulin or a sulfonylurea. The most common side effects are digestive, such as nausea, vomiting, diarrhea and constipation.
- This is a high-level summary, not a complete list. A licensed clinician will review your health history to decide whether a GLP-1 medication is right for you.
