Reviewed by a board-certified obesity medicine physician. Last updated March 2026.
The Core Distinction
These four brand names come from two active ingredients made by two manufacturers. Understanding this simplifies the comparison considerably.
Semaglutide (Novo Nordisk):
- Ozempic: FDA-approved for type 2 diabetes (December 2017). Max dose 2.0 mg weekly injection.
- Wegovy: FDA-approved for chronic weight management (June 2021). Max dose 2.4 mg weekly injection. Also available as a daily oral tablet (approved December 2025).
Tirzepatide (Eli Lilly):
- Mounjaro: FDA-approved for type 2 diabetes (May 2022). Max dose 15 mg weekly injection.
- Zepbound: FDA-approved for chronic weight management (November 2023). Max dose 15 mg weekly injection.
Ozempic and Wegovy contain the same molecule at different doses. Mounjaro and Zepbound contain the same molecule at the same doses. The FDA indication, not the chemistry, is what differs.
Head-to-Head Clinical Data
SURMOUNT-5: The Definitive Comparison
The SURMOUNT-5 trial is the first randomized, head-to-head study comparing tirzepatide and semaglutide for weight loss [1]. At 72 weeks, results showed:
- Tirzepatide (max dose): 20.2% average weight loss
- Semaglutide (2.4 mg): 13.7% average weight loss
The difference of 6.5 percentage points was statistically significant. For a 220-pound patient, that translates to roughly 44 pounds lost with tirzepatide versus 30 pounds with semaglutide.
Prior Trial Data
The landmark trials for each medication also provide useful context:
| Trial | Medication | Duration | Avg. Weight Loss | Published |
|---|---|---|---|---|
| STEP 1 [2] | Semaglutide 2.4 mg | 68 weeks | 14.9% | NEJM 2021 |
| STEP 2 [3] | Semaglutide 2.4 mg (T2D) | 68 weeks | 9.6% | Lancet 2021 |
| SURMOUNT-1 [4] | Tirzepatide 15 mg | 72 weeks | 22.5% | NEJM 2022 |
| SURMOUNT-2 [5] | Tirzepatide 15 mg (T2D) | 72 weeks | 14.7% | Lancet 2023 |
Cardiovascular Outcomes
The SELECT trial demonstrated that semaglutide reduces major cardiovascular events by 20% in adults with obesity and established cardiovascular disease [6]. No equivalent cardiovascular outcomes trial has been completed for tirzepatide, though the SURPASS-CVOT trial is underway.
Side Effect Comparison
Both medications share a similar gastrointestinal side effect profile. Rates from clinical trials:
| Side Effect | Semaglutide (Wegovy) | Tirzepatide (Zepbound) |
|---|---|---|
| Nausea | 44% | 24-33% |
| Diarrhea | 30% | 18-25% |
| Vomiting | 24% | 9-13% |
| Constipation | 24% | 11-17% |
Semaglutide shows higher reported nausea rates in trials, though real-world tolerability is broadly similar. Both medications cause side effects primarily during dose titration, with significant improvement over time.
Cost Comparison (2026)
| Medication | List Price/Month | Best Cash-Pay Option | With Savings Card |
|---|---|---|---|
| Ozempic | $935-$1,029 | Varies by pharmacy | $25/month (eligible) |
| Wegovy (injection) | $1,349-$1,650 | NovoCare: $499/month | $0-$25/month (eligible) |
| Wegovy (oral tablet) | $1,200-$1,400 | $149-$299/month | $0-$25/month (eligible) |
| Mounjaro | $1,023-$1,177 | Varies by pharmacy | $25/month (eligible) |
| Zepbound | $1,059-$1,177 | LillyDirect vials: $299-$449/month | $25/month (eligible) |
Manufacturer savings cards are available for commercially insured patients but cannot be used with Medicare, Medicaid, or Tricare.
Decision Framework
Choose semaglutide (Wegovy) if:
- You have established cardiovascular disease (SELECT trial evidence [6])
- You prefer an oral tablet option (oral Wegovy)
- Your insurance covers Wegovy but not Zepbound
- The NovoCare $499/month cash-pay price fits your budget
- You want the longer real-world safety record
Choose tirzepatide (Zepbound) if:
- Maximum weight loss is your primary goal (SURMOUNT-5 data [1])
- You also have type 2 diabetes (dual incretin benefits)
- Semaglutide was ineffective or poorly tolerated
- LillyDirect vials at $299-$449/month fit your budget
- Your insurance covers Zepbound
When the choice is unclear:
Start with whichever medication your insurance covers at the lowest copay. If both are covered equally, clinical data favors tirzepatide for weight loss. If one is intolerable, switching to the other is common and medically appropriate.
Search our provider directory to find clinics that prescribe both semaglutide and tirzepatide, so you and your provider can make the best choice together.
Medical Disclaimer: This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting any medication.
Sources
- Aronne LJ, et al. "Tirzepatide vs Semaglutide for Weight Loss." SURMOUNT-5 Trial. JAMA. 2024. ClinicalTrials.gov NCT05822609
- Wilding JPH, et al. "Once-Weekly Semaglutide in Adults with Overweight or Obesity." NEJM. 2021;384:989-1002. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
- Davies M, et al. "Semaglutide 2.4 mg in Adults with Overweight or Obesity and Type 2 Diabetes (STEP 2)." Lancet. 2021;397(10278):971-984. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00213-0/fulltext
- Jastreboff AM, et al. "Tirzepatide Once Weekly for the Treatment of Obesity." NEJM. 2022;387:205-216. https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
- Garvey WT, et al. "Tirzepatide for Treatment of Obesity in People With Type 2 Diabetes (SURMOUNT-2)." Lancet. 2023;402(10402):613-626. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01200-X/fulltext
- Lincoff AM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)." NEJM. 2023;389:2221-2232. https://www.nejm.org/doi/full/10.1056/NEJMoa2307563