Weight Management
Semaglutide vs Tirzepatide: What Patients Should Know
Semaglutide and tirzepatide are both once-weekly GLP-1-based medications used for weight management, and both are currently available. Here is how they compare.
Reviewed by the clinical team at Zest 4 Wellness · September 23, 2026 · 8 min read
Semaglutide (Wegovy, Ozempic) and tirzepatide (Zepbound, Mounjaro) are both prescription once-weekly injectable medications used for weight management, and both are currently available in the United States after the FDA declared their shortages resolved. They differ in how they work: semaglutide targets one receptor pathway and tirzepatide targets two. In the largest head-to-head trial, tirzepatide produced greater average weight loss than semaglutide, while side effect types were broadly similar. The right choice for any patient is made after a medical evaluation, not from comparing numbers alone.
How each medication works
Semaglutide is a GLP-1 receptor agonist: it mimics one gut hormone that helps regulate appetite and blood sugar. Tirzepatide is a dual agonist: it targets both the GLP-1 receptor and the GIP receptor, a second gut hormone pathway. This dual action is the main pharmacological difference between the two.
What the head-to-head data show
In the SURMOUNT-5 trial published in the New England Journal of Medicine in 2025, adults with obesity or overweight without diabetes were randomly assigned to tirzepatide or semaglutide at maximum tolerated doses for 72 weeks. Mean weight loss was 20.2% for tirzepatide versus 13.7% for semaglutide, roughly 47% greater relative weight loss. More patients in the tirzepatide group reached 10%, 15%, 20%, and 25% weight loss thresholds. For context, placebo-controlled trials of semaglutide have shown roughly 15% mean weight loss, and tirzepatide studies around 20%, versus placebo.
| Medication | Mechanism | Once-weekly dosing | 72-week mean weight loss in SURMOUNT-5 |
|---|---|---|---|
| Semaglutide (Wegovy) | GLP-1 receptor agonist | Yes, titrated to maintenance | 13.7% |
| Tirzepatide (Zepbound) | Dual GLP-1 and GIP agonist | Yes, titrated to maintenance | 20.2% |
Side effects and tolerance
Both medications share a similar class of side effects, mostly gastrointestinal: nausea, vomiting, diarrhea, constipation, and abdominal discomfort, especially during dose increases. In meta-analyses, average weight loss favors tirzepatide by roughly four percentage points, while some analyses report a higher rate of serious adverse events with tirzepatide even as overall and gastrointestinal side effects look similar. Slow titration under supervision is how most patients manage these effects.
Availability and supply status
Both medications are currently available in the United States. The tirzepatide shortage was declared resolved in December 2024 and the semaglutide shortage on February 21, 2025. Because compounding of copies was tied to shortage status, large-scale compounding has wound down; patients should be cautious about programs still built on compounded products. Read more in our guide to compounded GLP-1 medications.
Which one may be appropriate for you
Trial averages describe groups, not individuals. Which medication, if any, is appropriate depends on your health history, how you tolerate dose increases, your goals, and what your evaluation shows. At Zest 4 Wellness in Columbia, Maryland, GLP-1 medications are considered within a supervised weight loss program: evaluation first, testing when it informs the plan, dosing guidance, and scheduled follow-up.
Meet Dr. Francisco Ward, who evaluates patients at Zest 4 Wellness (/dr-francisco-ward/).
Sources & further reading
Next step
Trial data is useful background, but your plan starts with your evaluation. Book a free 15-minute consultation at the Columbia clinic and the team will explain which options may be appropriate for you, what monitoring looks like, and what to expect from a supervised program.
Talk with our care team about this topic
A member of our clinical team can answer your questions at the Columbia, Maryland clinic. If GLP-1 Weight Loss Programs may be appropriate for you, the first step is a consultation.
Care at Zest 4 Wellness is physician-guided. Meet Dr. Francisco Ward, who evaluates patients at the Columbia, Maryland clinic.