Switching from Zepbound (Tirzepatide) 2.5mg/0.5mL to Wegovy (Semaglutide)
When transitioning from Zepbound 2.5mg/0.5mL to Wegovy, start directly with Wegovy 0.25mg weekly for 4 weeks, then follow the standard Wegovy dose escalation protocol regardless of previous tirzepatide dosing. 1
Rationale for Switching
Both medications are injectable weight management therapies, but they work through different mechanisms:
- Zepbound (tirzepatide): Dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist
- Wegovy (semaglutide): Selective GLP-1 receptor agonist only
Key differences to consider:
- Tirzepatide generally produces greater weight loss than semaglutide (20.9% vs 9.6% at maximum doses) 1
- Both medications have similar safety profiles with primarily gastrointestinal side effects 1
Transition Protocol
Discontinue Zepbound:
- Stop Zepbound (tirzepatide) 2.5mg/0.5mL injections
- No washout period is required between medications
Initiate Wegovy:
- Start with Wegovy 0.25mg subcutaneous injection once weekly for 4 weeks
- Follow the standard dose escalation protocol:
- 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 and onward: 2.4mg once weekly (maintenance dose)
Monitor During Transition:
- Watch for gastrointestinal side effects (nausea, vomiting, diarrhea)
- Monitor for potential consequences of delayed gastric emptying
- Assess weight response and tolerance at each dose escalation
Important Clinical Considerations
- Dose Titration: Always follow the gradual dose escalation schedule for Wegovy to minimize gastrointestinal side effects 1
- Efficacy Expectations: Patients may experience less weight loss with Wegovy compared to Zepbound (9.6% vs 14.7-20.9% weight reduction) 1
- Side Effect Profile: Both medications have similar side effects, primarily gastrointestinal in nature 1
- Contraception: Advise females using oral contraceptives to switch to a non-oral method due to potential delayed absorption of oral medications 1
- Contraindications: Do not use in individuals with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 1
Monitoring Recommendations
- Assess for gastrointestinal side effects 4 weeks after initiation and for 4 weeks after each dose escalation
- Monitor for potential gallbladder-related complications
- Watch for signs of pancreatitis, which has been associated with both GLP-1 receptor agonists
- Be alert for potential injection site reactions
The transition from Zepbound to Wegovy should follow the standard Wegovy initiation protocol regardless of previous tirzepatide exposure, as this approach minimizes gastrointestinal side effects and ensures optimal safety and efficacy.