Switching from Zepbound 7.5 mg Weekly to Wegovy
When switching from tirzepatide (Zepbound) 7.5 mg weekly to semaglutide (Wegovy), discontinue tirzepatide and initiate semaglutide at 0.25 mg weekly the following week, then follow the standard 16-week titration schedule to reach the maintenance dose of 2.4 mg weekly. 1
Direct Switching Protocol
You must start at the lowest dose of semaglutide (0.25 mg weekly) regardless of your prior tirzepatide dose. 1 This is not negotiable—the standard titration must be followed to minimize gastrointestinal adverse effects, even though you were on a higher dose of tirzepatide. 1
Specific Titration Schedule
Follow this exact weekly dosing schedule after discontinuing Zepbound: 1, 2
- Weeks 1-4: Semaglutide 0.25 mg subcutaneously once weekly
- Weeks 5-8: Semaglutide 0.5 mg subcutaneously once weekly
- Weeks 9-12: Semaglutide 1.0 mg subcutaneously once weekly
- Weeks 13-16: Semaglutide 1.7 mg subcutaneously once weekly
- Week 17 onwards: Semaglutide 2.4 mg subcutaneously once weekly (maintenance dose)
Critical Safety Considerations
Absolute contraindications that must be ruled out before switching: 1
- Personal or family history of medullary thyroid cancer
- Multiple endocrine neoplasia syndrome type 2
Do not combine semaglutide with other GLP-1 receptor agonists or DPP-4 inhibitors. 1 This means you cannot overlap tirzepatide and semaglutide—stop one completely before starting the other.
What to Expect During the Switch
Gastrointestinal Effects
Expect nausea (18-40% of patients), diarrhea (12%), and vomiting (8-16%) during dose escalation, typically mild-to-moderate and transient. 1 These effects occur even though you tolerated tirzepatide, because semaglutide has a different receptor profile and the gradual titration is essential for tolerance.
Weight Loss Trajectory
You will likely experience continued weight loss, though potentially less than with tirzepatide. 1 Semaglutide 2.4 mg achieves 14.9% weight loss at 68 weeks compared to tirzepatide's 20.9% at 72 weeks—a 6% absolute difference. 1
Monitoring Schedule
- Every 4 weeks during titration (first 16 weeks): Assess gastrointestinal tolerance, weight loss progress, and blood pressure 1
- Every 3 months after reaching maintenance dose: Monitor weight, cardiovascular risk factors, and medication adherence 1
Why This Approach Is Necessary
The pharmacologic mechanisms differ between tirzepatide and semaglutide despite both being incretin-based therapies. 1 Tirzepatide activates both GIP and GLP-1 receptors, while semaglutide is a selective GLP-1 receptor agonist with greater albumin affinity. 1 This means your body needs to adapt to the different receptor activation pattern, requiring the full titration schedule.
Potential Advantages of Switching to Semaglutide
If you have established cardiovascular disease, semaglutide offers proven cardiovascular benefit with a 20% reduction in cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80). 1 This is a key advantage over tirzepatide, which has not yet demonstrated this specific cardiovascular outcome benefit in completed trials.
Common Pitfall to Avoid
Do not attempt to "dose-match" or start at a higher semaglutide dose based on your tirzepatide dose. 1 The medications are not interchangeable on a mg-to-mg basis, and skipping the titration schedule dramatically increases the risk of intolerable gastrointestinal side effects leading to treatment discontinuation.
Administration Details
Semaglutide can be administered at any time of day, with or without meals. 2 If you miss a dose and it has been less than 5 days, administer as soon as possible; if more than 5 days have passed, skip the missed dose and resume your regular schedule. 2