Switching from Zepbound 10mg to Wegovy: Direct Protocol
You should order Wegovy 0.25mg weekly and follow the standard 16-week titration schedule, starting from the beginning regardless of the patient's current Zepbound dose. 1, 2
Critical Understanding: No Direct Dose Equivalency
There is no established dose conversion between tirzepatide (Zepbound) and semaglutide (Wegovy) because they have fundamentally different mechanisms of action 3:
- Tirzepatide activates both GIP and GLP-1 receptors, with approximately 5 times less affinity for GLP-1 receptors than endogenous GLP-1 3
- Semaglutide is a selective GLP-1 receptor agonist with greater albumin affinity and prolonged action 3
You cannot simply "match" doses between these medications - the patient must restart titration from the beginning 1.
Standard Wegovy Titration Schedule
Follow this FDA-approved schedule regardless of prior Zepbound dose 1, 2:
- Weeks 1-4: 0.25mg once weekly
- Weeks 5-8: 0.5mg once weekly
- Weeks 9-12: 1.0mg once weekly
- Weeks 13-16: 1.7mg once weekly
- Week 17 onward: 2.4mg once weekly (maintenance dose)
The gradual titration is essential to minimize gastrointestinal adverse effects (nausea, vomiting, diarrhea), which occur in the majority of patients 1, 4.
Switching Protocol
Discontinue Zepbound completely and start Wegovy 0.25mg the following week 3. Do not overlap these medications - combining GLP-1 receptor agonists is contraindicated due to overlapping mechanisms and potential harm 3.
What to Expect with the Switch
Weight Loss Efficacy
- Zepbound 10mg achieves approximately 20.9% weight loss at 72 weeks 3
- Wegovy 2.4mg achieves 14.9% weight loss at 68 weeks 3, 5, 6
- The patient may experience less weight loss with Wegovy compared to their current Zepbound regimen, representing approximately a 6% absolute difference 3
Potential Advantages of Wegovy
- Proven cardiovascular benefit: 20% reduction in cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80) in patients with established cardiovascular disease 3, 2
- If your patient has cardiovascular disease, this may justify the switch despite lower weight loss efficacy 3
Side Effects During Transition
- The patient will likely experience gastrointestinal symptoms again during the initial titration weeks, even though they tolerated Zepbound 1, 4
- Nausea occurs in 18-40% of patients on semaglutide 3
- These symptoms are typically mild-to-moderate and transient, decreasing over time 3, 4
Concomitant Medication Adjustments
If the patient is taking other diabetes medications 3, 2:
- Reduce basal insulin by 20% when starting Wegovy to prevent hypoglycemia 3
- Discontinue or reduce sulfonylureas by 50% to prevent hypoglycemia 3
- Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors 3
Monitoring During Transition
- Every 4 weeks during titration for gastrointestinal tolerance, weight, and blood pressure
- At 12-16 weeks on the maximum tolerated dose to evaluate efficacy
- Every 3 months after reaching maintenance dose for weight stability, cardiovascular risk factors, and medication adherence
Critical Contraindications
Do not prescribe Wegovy if the patient has 3, 2:
- Personal or family history of medullary thyroid cancer
- Multiple endocrine neoplasia syndrome type 2 (MEN2)
- Known hypersensitivity to semaglutide
Common Pitfall to Avoid
Do not attempt to start at a higher Wegovy dose (like 1.0mg or 1.7mg) based on the patient's tolerance of Zepbound 10mg 1. The medications have different receptor profiles and pharmacokinetics - starting at higher doses dramatically increases the risk of severe gastrointestinal adverse events leading to treatment discontinuation 1, 4.