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Tirzepatide vs. semaglutide: how the two GLP-1 medicines compare
Published · Editorial team
Medical review pending · Last updated
Semaglutide and tirzepatide are the two most widely prescribed medicines for chronic weight management in the U.S. Both are once-weekly injections approved by the FDA for adults with obesity, or overweight with at least one weight-related condition, alongside a reduced-calorie diet and more physical activity. They are related, but not identical.
How they work
Semaglutide (the active ingredient in Wegovy® and, for type 2 diabetes, Ozempic®) mimics one gut hormone, GLP-1. It slows stomach emptying and acts on appetite centers in the brain.
Tirzepatide (Zepbound® for weight management; Mounjaro® for type 2 diabetes) acts on two hormone receptors, GLP-1 and GIP. That dual action is the main pharmacological difference.
What the trials showed
In their pivotal trials, both medicines produced meaningfully more weight loss than placebo over about 68 to 72 weeks. In a 2025 head-to-head trial (SURMOUNT-5) published in the New England Journal of Medicine, adults taking tirzepatide lost more weight on average than those taking semaglutide. Averages are not predictions: individual results vary widely, and some people lose little weight on either medicine.
Side effects
Both share the same class side effects, mostly gastrointestinal: nausea, diarrhea, vomiting, and constipation, which are usually most noticeable while the dose is increasing. Both carry a boxed warning about thyroid C-cell tumors seen in rodents. Serious but less common risks include pancreatitis and gallbladder disease. See the important safety information.
Forms and schedules
| Semaglutide (Wegovy®) | Tirzepatide (Zepbound®) | |
|---|---|---|
| Targets | GLP-1 | GLP-1 + GIP |
| Forms | Weekly injection; once-daily tablet (Wegovy® pill, approved Dec 2025) | Weekly injection (pens and single-dose vials) |
| Other approved uses | Reduce major cardiovascular events in adults with established heart disease and obesity/overweight; MASH (liver) | Moderate-to-severe obstructive sleep apnea in adults with obesity |
Which one is right for you?
That depends on your health history, other conditions, side-effect tolerance, cost, and access. Only a licensed provider can decide whether either is appropriate. Bring your questions, current medications, and goals to that conversation.
Sources
- FDA-approved prescribing information: Wegovy (semaglutide) injection and tablets (DailyMed, NLM)
- FDA-approved prescribing information: Zepbound (tirzepatide) injection (DailyMed, NLM)
- Aronne LJ et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med 2025 (PubMed)
- Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med 2021 (PubMed)
- Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med 2022 (PubMed)
Sources are listed for reference and do not imply endorsement. Regulatory status can change; check the date above.
This article is for education only and is not medical or legal advice. A licensed clinician decides whether any treatment is appropriate for you.