Tirzepatide vs Semaglutide: Side-by-Side Comparison
Tirzepatide and Semaglutide are among the most discussed weight loss compounds in development and on the market. Both target overlapping metabolic pathways — but their receptor targets, approval status, and clinical data tell meaningfully different stories.
The core difference: Tirzepatide is a gip/glp-1 dual receptor agonist, while Semaglutide is a glp-1 receptor agonist. This receptor targeting difference explains why their weight loss outcomes and side effect profiles diverge — even though both work within the incretin hormone system.
Tirzepatide
AKA: Mounjaro, Zepbound, LY3298176
FDA-approved dual-action peptide delivering up to 22% weight loss — the gold standard of prescription weight management.
FDA ApprovedSemaglutide
AKA: Ozempic, Wegovy, Rybelsus
The peptide that started the weight loss revolution — FDA-approved, clinically proven, and widely accessible.
FDA ApprovedHead-to-Head Comparison
| Category | Tirzepatide | Semaglutide |
|---|---|---|
| Class | GIP/GLP-1 Dual Receptor Agonist | GLP-1 Receptor Agonist |
| Typical Dose | 10-15 mg Once weekly | 1.7-2.4 mg Once weekly (injectable); once daily (Rybelsus oral) |
| Half-Life | ~5 days | ~7 days |
| Administration | Subcutaneous injection (abdomen, thigh, upper arm) | Subcutaneous injection (abdomen, thigh, upper arm), Oral tablet (Rybelsus) |
| FDA Approval | FDA approved for T2D (Mounjaro, 2022) and obesity (Zepbound, 2023)✓ Edge | FDA approved for T2D (Ozempic, 2017), obesity (Wegovy, 2021), CV risk reduction (2023), oral T2D (Rybelsus, 2019) |
| Primary Uses | Type 2 diabetes (Mounjaro), Weight loss/obesity (Zepbound), Cardiovascular risk reduction | Type 2 diabetes (Ozempic), Weight loss/obesity (Wegovy), Cardiovascular risk reduction (SELECT trial) |
| Legal Status | FDA approved. Requires prescription. Available via physician or telehealth provider. | FDA approved. Requires prescription. Widely available through physicians and telehealth. |
Clinical Trial Outcomes: What the Data Shows
The following data comes from Phase 2/3 trials. These trials used different populations, durations, and endpoints — direct comparison is directional, not definitive.
| Metric | Tirzepatide | Semaglutide |
|---|---|---|
| Drug class | GIP/GLP-1 Dual Receptor Agonist | GLP-1 Receptor Agonist |
| Peak weight loss (mean, max dose) | 20.9% (72 weeks) | 14.9% (68 weeks) |
| Trial population | N=2539, SURMOUNT-1 | N=1961, STEP 1 |
| FDA approval (obesity) | Approved | Approved |
| Thermogenesis mechanism | Minimal | Minimal |
Tirzepatide data: New England Journal of Medicine, 2022. DOI: 10.1056/NEJMoa2206038
Side Effects Comparison
Tirzepatide
Semaglutide
Both Used For
Who Should Choose Which?
Choose Tirzepatide if:
- • You want type 2 diabetes (mounjaro)
- • You want an FDA-approved option
- • Subcutaneous injection (abdomen, thigh, upper arm) is your preferred route
Choose Semaglutide if:
- • You want type 2 diabetes (ozempic)
- • You want an FDA-approved option available by prescription today
- • Subcutaneous injection (abdomen, thigh, upper arm) is your preferred route
- • You need immediate access — pharmacy-dispensed, insurance-eligible, telehealth available
Switching From One to the Other
If you are currently on Semaglutide and considering switching to Tirzepatide (or vice versa), here is what to plan for:
Switching from Semaglutide to Tirzepatide
- • Eligibility: Discuss with your prescribing physician.
- • Washout: Weekly GLP-1 drugs typically require 4–8 weeks washout due to extended half-lives (~7 days). Overlapping two GLP-class drugs increases GI side effect risk.
- • Re-titration: Start at the lowest dose of the new drug and re-titrate — even if you tolerated high doses of the previous drug.
- • Expect adjustment: 4–12 weeks for full receptor adaptation to the new molecule.
Switching from Tirzepatide to Semaglutide
- • Access: Semaglutide is FDA approved and available by prescription.
- • Washout: Same 4–8 week washout principle applies — allow the first drug to clear before starting the second.
- • Weight: Expect some weight regain during the washout period as appetite normalizes without active drug coverage.
- • Indication: Ensure Semaglutide is appropriate for your indication — approval status and coverage differ.
Frequently Asked Questions
What is the main difference between Tirzepatide and Semaglutide?
Tirzepatide (GIP/GLP-1 Dual Receptor Agonist) and Semaglutide (GLP-1 Receptor Agonist) differ in their receptor targets, mechanism of action, and clinical applications. Tirzepatide: FDA-approved dual-action peptide delivering up to 22% weight loss — the gold standard of prescription weight management. Semaglutide: The peptide that started the weight loss revolution — FDA-approved, clinically proven, and widely accessible.
Which is better for weight loss — Tirzepatide or Semaglutide?
In direct trial comparisons, Tirzepatide showed 20.9% mean weight loss at peak dose (72 weeks), while Semaglutide trial data shows different outcomes. Weight loss superiority depends on dose, duration, and individual response. Consult a healthcare provider to determine which is appropriate.
Can you take Tirzepatide and Semaglutide together?
Combining Tirzepatide and Semaglutide has not been studied in clinical trials and is not recommended without direct medical supervision. The pharmacological overlap between them may increase the risk of side effects.
Is Tirzepatide stronger than Semaglutide?
Based on TRIUMPH-1 trial data, Tirzepatide at 24mg produced 20.9% mean weight loss at 72 weeks — the highest recorded for any injectable weight loss drug in a clinical trial at the time. However, Semaglutide is FDA approved and commercially available, while Tirzepatide remains investigational. Potency in trials and real-world access are different considerations.
Which should I choose — Tirzepatide or Semaglutide?
The choice depends on your specific goals, medical history, cost considerations, and physician guidance. Review the mechanism, dosing, and side effect profiles of each with a healthcare provider before deciding.
Can I switch from Semaglutide to Tirzepatide?
Switching between GLP-class drugs is possible but requires a washout period and physician oversight. For weekly injectable GLP-1 drugs, a typical washout is 4–8 weeks due to the extended half-life. Switching while Tirzepatide remains investigational is not a standard clinical option — you would need to enroll in a clinical trial or wait for FDA approval. Discuss transition planning with your prescribing physician.