Semaglutide vs Tirzepatide: Side-by-Side Comparison
Semaglutide and Tirzepatide 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: Semaglutide is a glp-1 receptor agonist, while Tirzepatide is a gip/glp-1 dual 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.
Semaglutide
AKA: Ozempic, Wegovy, Rybelsus
The peptide that started the weight loss revolution — FDA-approved, clinically proven, and widely accessible.
FDA ApprovedTirzepatide
AKA: Mounjaro, Zepbound, LY3298176
FDA-approved dual-action peptide delivering up to 22% weight loss — the gold standard of prescription weight management.
FDA ApprovedHead-to-Head Comparison
| Category | Semaglutide | Tirzepatide |
|---|---|---|
| Class | GLP-1 Receptor Agonist | GIP/GLP-1 Dual Receptor Agonist |
| Typical Dose | 1.7-2.4 mg Once weekly (injectable); once daily (Rybelsus oral) | 10-15 mg Once weekly |
| Half-Life | ~7 days | ~5 days |
| Administration | Subcutaneous injection (abdomen, thigh, upper arm), Oral tablet (Rybelsus) | Subcutaneous injection (abdomen, thigh, upper arm) |
| FDA Approval | FDA approved for T2D (Ozempic, 2017), obesity (Wegovy, 2021), CV risk reduction (2023), oral T2D (Rybelsus, 2019)✓ Edge | FDA approved for T2D (Mounjaro, 2022) and obesity (Zepbound, 2023) |
| Primary Uses | Type 2 diabetes (Ozempic), Weight loss/obesity (Wegovy), Cardiovascular risk reduction (SELECT trial) | Type 2 diabetes (Mounjaro), Weight loss/obesity (Zepbound), Cardiovascular risk reduction |
| Legal Status | FDA approved. Requires prescription. Widely available through physicians and telehealth. | FDA approved. Requires prescription. Available via physician or telehealth provider. |
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 | Semaglutide | Tirzepatide |
|---|---|---|
| Drug class | GLP-1 Receptor Agonist | GIP/GLP-1 Dual Receptor Agonist |
| Peak weight loss (mean, max dose) | 14.9% (68 weeks) | 20.9% (72 weeks) |
| Trial population | N=1961, STEP 1 | N=2539, SURMOUNT-1 |
| FDA approval (obesity) | Approved | Approved |
| Thermogenesis mechanism | Minimal | Minimal |
Semaglutide data: New England Journal of Medicine, 2021. DOI: 10.1056/NEJMoa2032183
Side Effects Comparison
Semaglutide
Tirzepatide
Both Used For
Who Should Choose Which?
Choose Semaglutide if:
- • You want type 2 diabetes (ozempic)
- • You want an FDA-approved option
- • Subcutaneous injection (abdomen, thigh, upper arm) is your preferred route
Choose Tirzepatide if:
- • You want type 2 diabetes (mounjaro)
- • 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 Tirzepatide and considering switching to Semaglutide (or vice versa), here is what to plan for:
Switching from Tirzepatide to Semaglutide
- • 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 Semaglutide to Tirzepatide
- • Access: Tirzepatide 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 Tirzepatide is appropriate for your indication — approval status and coverage differ.
Frequently Asked Questions
What is the main difference between Semaglutide and Tirzepatide?
Semaglutide (GLP-1 Receptor Agonist) and Tirzepatide (GIP/GLP-1 Dual Receptor Agonist) differ in their receptor targets, mechanism of action, and clinical applications. Semaglutide: The peptide that started the weight loss revolution — FDA-approved, clinically proven, and widely accessible. Tirzepatide: FDA-approved dual-action peptide delivering up to 22% weight loss — the gold standard of prescription weight management.
Which is better for weight loss — Semaglutide or Tirzepatide?
In direct trial comparisons, Semaglutide showed 14.9% mean weight loss at peak dose (68 weeks), while Tirzepatide 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 Semaglutide and Tirzepatide together?
Combining Semaglutide and Tirzepatide 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 Semaglutide stronger than Tirzepatide?
Based on TRIUMPH-1 trial data, Semaglutide at 24mg produced 14.9% mean weight loss at 68 weeks — the highest recorded for any injectable weight loss drug in a clinical trial at the time. However, Tirzepatide is FDA approved and commercially available, while Semaglutide remains investigational. Potency in trials and real-world access are different considerations.
Which should I choose — Semaglutide or Tirzepatide?
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 Tirzepatide to Semaglutide?
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 Semaglutide 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.