Switching from Zepbound 15 mg to Wegovy: Dosing Strategy
When switching from tirzepatide (Zepbound) 15 mg to semaglutide (Wegovy), you should follow Wegovy's standard dose titration schedule starting at 0.25 mg weekly, regardless of prior GLP-1 RA exposure.
Rationale for Complete Dose Titration
Despite both medications being GLP-1 receptor agonists, there are important differences that necessitate following the full titration schedule:
Different mechanisms of action:
- Tirzepatide (Zepbound) is a dual GIP/GLP-1 receptor agonist
- Semaglutide (Wegovy) is a selective GLP-1 receptor agonist
FDA labeling requirements:
- Wegovy's FDA label explicitly states the need to follow the dose escalation schedule to reduce gastrointestinal adverse reactions 1
Different pharmacokinetic profiles:
- Tirzepatide has a half-life of approximately 5 days
- Semaglutide has a half-life of approximately 7 days 2
Recommended Titration Schedule for Wegovy
Follow this specific titration schedule when switching from Zepbound to Wegovy:
| Treatment Weeks | Once-weekly Subcutaneous Dosage |
|---|---|
| 1 through 4 | 0.25 mg |
| 5 through 8 | 0.5 mg |
| 9 through 12 | 1 mg |
| 13 through 16 | 1.7 mg |
| 17 and onward | 2.4 mg (or 1.7 mg if needed) |
Important Clinical Considerations
Managing Gastrointestinal Side Effects
- GI side effects are the most common adverse events with both medications
- Gradual dose titration is specifically designed to minimize nausea, vomiting, and diarrhea 2
- If GI symptoms become intolerable during titration:
- Consider delaying dose escalation for 4 weeks
- Do not skip the titration steps, as this increases risk of GI adverse effects
Timing of Switch
- No washout period is required between medications
- Start Wegovy the week after the last Zepbound dose
- Maintain the same weekly injection day if possible for consistency
Monitoring During Transition
- Monitor blood glucose levels more frequently during the transition, especially in patients with diabetes 1
- Be alert for potential hypoglycemia if the patient is on other glucose-lowering medications
- Weight may temporarily plateau or slightly increase during the initial titration period due to the lower starting dose of Wegovy
Special Considerations
Dosing in Renal Impairment
- No dose adjustment is required for Wegovy in patients with renal impairment, including end-stage renal disease 2
Perioperative Management
- If elective surgery is planned during the transition period, consider the timing of the switch due to potential effects on gastric emptying 2
Missed Doses
- If one dose is missed and the next scheduled dose is >48 hours away, administer Wegovy as soon as possible
- If one dose is missed and the next scheduled dose is <48 hours away, skip the missed dose
- If ≥2 consecutive doses are missed, restart the titration schedule from the beginning 1
Common Pitfalls to Avoid
- Skipping titration steps: This significantly increases the risk of GI side effects and may lead to treatment discontinuation
- Assuming equivalent dosing: Despite both being GLP-1 RAs, direct dose conversion is not appropriate
- Overlapping medications: Do not use Wegovy concurrently with other GLP-1 RAs, including Zepbound 1
- Inadequate patient education: Ensure patients understand the need for complete titration despite prior GLP-1 RA experience
By following this structured approach to switching from Zepbound to Wegovy, you can maximize treatment success while minimizing adverse effects.