How they work
Both drugs copy hormones your gut releases after you eat. They slow how fast your stomach empties, help your pancreas release insulin when blood sugar is high, and act on the brain to reduce appetite.
- Semaglutide is a GLP-1 receptor agonist. It acts on the GLP-1 receptor only.
- Tirzepatide is a dual GIP and GLP-1 receptor agonist. It acts on the GLP-1 receptor and also on the receptor for GIP, a second gut hormone involved in insulin release and fat storage. The FDA describes it as activating receptors for both hormones.
Researchers think the added GIP action is part of why tirzepatide produced more weight loss in trials, though exactly how it contributes is still being studied.
Brand names and approved uses
| Brand | Medication | Form | Main FDA-approved uses |
|---|---|---|---|
| Wegovy | Semaglutide | Weekly injection or daily pill | Chronic weight management; lowering the risk of heart attack, stroke and cardiovascular death in adults with heart disease and obesity or overweight; injection only: MASH, a fatty liver disease, with moderate to advanced liver scarring but not cirrhosis, in adults |
| Ozempic | Semaglutide | Weekly injection or daily pill | Type 2 diabetes |
| Zepbound | Tirzepatide | Weekly injection (pen, KwikPen or vial) | Chronic weight management; moderate to severe obstructive sleep apnea in adults with obesity |
| Mounjaro | Tirzepatide | Weekly injection | Type 2 diabetes |
What head-to-head trials found
Two large randomized trials, both funded by tirzepatide's manufacturer and both open-label (participants knew which drug they got), compared the two directly. Both tested the manufacturers' own medicines, not compounded versions.
- Weight: SURMOUNT-5 (NEJM, 2025). 751 adults with obesity but without type 2 diabetes took the highest dose they tolerated of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) once a week for 72 weeks. Average weight change was 20.2% with tirzepatide and 13.7% with semaglutide. Waist size fell 18.4 cm and 13.0 cm. More people on tirzepatide reached 10%, 15%, 20% and 25% weight loss.
- Diabetes: SURPASS-2 (NEJM, 2021). 1,879 adults with type 2 diabetes took tirzepatide (5, 10 or 15 mg) or semaglutide (1 mg) weekly for 40 weeks. HbA1c fell 2.01 to 2.30 percentage points with tirzepatide and 1.86 with semaglutide. Tirzepatide groups lost 1.9 to 5.5 kg more weight than the semaglutide group.
SURPASS-2 used 1 mg of semaglutide, lower than the 2 mg Ozempic dose and the 2.4 mg Wegovy dose available today, so it doesn't show how the drugs compare at semaglutide's highest doses for diabetes. Averages also hide a wide range: some people lose more on semaglutide than others do on tirzepatide.
Side effects and dosing schedule
The most common side effects of both are stomach-related: nausea, diarrhea, vomiting and constipation. In both trials, most were mild to moderate; in SURMOUNT-5 they happened mostly while the dose was being raised. In SURPASS-2, nausea affected 17% to 22% of people on tirzepatide and 18% on semaglutide.
- Both start at a low dose that a clinician raises step by step over weeks to months, which helps with tolerance.
- Injections of both are taken once a week. The Wegovy and Ozempic pills are taken once a day.
- Less common but serious risks listed for both include pancreatitis, gallbladder problems, low blood sugar when combined with insulin or sulfonylureas, and kidney problems from dehydration. Both labels carry a boxed warning about thyroid C-cell tumors seen in rodents.
Get medical care right away for severe stomach pain that doesn't go away (with or without vomiting), signs of an allergic reaction, a lump or swelling in your neck, or trouble swallowing. Don't change or stop a dose without talking to your clinician.
Cost
| Option | Monthly price |
|---|---|
| Wegovy injection, manufacturer self-pay | $349 ($399 for Wegovy HD 7.2 mg); new patients pay $199 for each of the first two fills at 0.25 or 0.5 mg through 12/31/2026 |
| Wegovy pill, manufacturer self-pay | $149 to $299 by dose |
| Zepbound vial or KwikPen, manufacturer self-pay | $299 to $449 with a refill within 45 days; up to $699 otherwise |
| Mounjaro, manufacturer self-pay | $499 |
| Compounded semaglutide through Gabriel | $89 to $116 by dose with a free account; from $87 with Gabriel Core or $84 with Plus |
| Compounded tirzepatide through Gabriel | $135 to $225 by dose with a free account; $131 to $218 with Gabriel Core, $128 to $213 with Plus |
Compounded medications aren't FDA-approved. A licensed clinician decides what's right for you.
With insurance, costs depend on your plan and diagnosis. See how much tirzepatide costs and how much GLP-1 medications cost for coverage, Medicare and savings card details.
Which one is right for you
Trials show tirzepatide produced more weight loss on average, but the better medication for one person depends on things a trial can't answer: your other conditions, past response to a GLP-1, side effects, other medications, and what your coverage pays for. A licensed clinician weighs those with you.
Through Gabriel, you can send a prescription request. A licensed clinician reviews it and decides whether either medication is appropriate.
Common questions
Is tirzepatide better than semaglutide?
In head-to-head trials, tirzepatide led to more average weight loss and a larger drop in HbA1c. That doesn't make it the right choice for everyone; side effects, health history and cost matter, and a clinician decides.
What is the difference between semaglutide and tirzepatide?
Semaglutide acts on the GLP-1 receptor. Tirzepatide acts on both the GIP and GLP-1 receptors. Semaglutide is sold as Wegovy and Ozempic; tirzepatide as Zepbound and Mounjaro.
Does tirzepatide have more side effects than semaglutide?
The side effects are similar and mostly stomach-related. In SURPASS-2, rates of nausea, diarrhea and vomiting were in a similar range for both drugs.
Can you switch from semaglutide to tirzepatide?
People do switch, for reasons like side effects, results or cost. A clinician decides whether to switch and what dose to start, so don't change on your own.
Which is cheaper, semaglutide or tirzepatide?
Without insurance, brand semaglutide (Wegovy) and brand tirzepatide (Zepbound) self-pay prices overlap, depending on dose. Through Gabriel, with a free account, compounded semaglutide is $89 to $116 a month and compounded tirzepatide is $135 to $225, depending on the dose; compounded medications aren't FDA-approved. A licensed clinician decides what's right for you.
Sources
- Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (Aronne et al., SURMOUNT-5, 2025) New England Journal of Medicine
- Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (Frías et al., SURPASS-2, 2021) New England Journal of Medicine
- FDA approves first medication for obstructive sleep apnea U.S. Food and Drug Administration
- FDA's concerns with unapproved GLP-1 drugs used for weight loss U.S. Food and Drug Administration
- NovoCare Pharmacy self-pay prices Novo Nordisk
- Zepbound coverage and savings Eli Lilly and Company
This guide is general information, not medical advice. It does not replace a visit with a licensed clinician. Gabriel membership is not health insurance.