What is the recommended protocol for transitioning a patient from dulaglutide (Trulicity) 4.5mg to tirzepatide (Mounjaro)?

Transitioning from Dulaglutide 4.5mg to Tirzepatide (Mounjaro)

When transitioning from dulaglutide (Trulicity) 4.5mg to tirzepatide (Mounjaro), start with tirzepatide 2.5mg weekly for 4 weeks, then follow the standard dose escalation protocol regardless of the previous dulaglutide dose.

Transition Protocol

Initial Transition

• Discontinue dulaglutide 4.5mg
• Start tirzepatide at 2.5mg weekly for 4 weeks
• No overlap period is required between medications

Dose Escalation Schedule

1. Week 1-4: 2.5mg weekly (initiation dose)
2. Week 5-8: Increase to 5mg weekly
3. Week 9-12: Increase to 7.5mg weekly (if needed)
4. Week 13-16: Increase to 10mg weekly (if needed)
5. Week 17+: Increase to 12.5mg and then 15mg weekly (if needed)

Monitoring Schedule

• Assess tolerance and glycemic response at 4 weeks after initiation
• Continue monitoring at least quarterly thereafter
• Evaluate for weight loss, glycemic control, and side effects

Rationale for This Approach

Tirzepatide is a dual GIP/GLP-1 receptor agonist with greater potency than dulaglutide (GLP-1 receptor agonist only). Despite coming from dulaglutide at a high dose (4.5mg), the standard titration protocol for tirzepatide must be followed to minimize gastrointestinal side effects 1.

Clinical studies have demonstrated that switching from dulaglutide to tirzepatide results in:

• Additional HbA1c reduction (average 1.2% further reduction)
• Enhanced weight loss (average 3.6kg additional loss)
• Potential improvements in liver function parameters 2

In a randomized controlled trial comparing tirzepatide to dulaglutide in Japanese patients, all doses of tirzepatide (5mg, 10mg, 15mg) showed superior glycemic control compared to dulaglutide 0.75mg, with estimated treatment differences of -1.1%, -1.3%, and -1.5% respectively 3.

Managing Side Effects During Transition

Gastrointestinal side effects are common during initiation and dose escalation:

• Most common side effects:
  • Nausea (31%)
  • Diarrhea (23%)
  • Vomiting (12%)
  • Constipation (5%)
  • Abdominal pain (5%) 1

Side Effect Management Strategies

• Reduce meal size during transition period
• Limit alcohol and carbonated beverages
• Avoid high-fat diets
• Consider antiemetics (e.g., ondansetron) for significant nausea
• Use loperamide for troublesome diarrhea

Special Considerations

• Renal impairment: No dose adjustment required, even in end-stage renal disease 1
• Pancreatitis risk: Monitor for severe abdominal pain, persistent nausea/vomiting, or elevated lipase 1, 4
• Surgical procedures: Consider stopping tirzepatide at least one week before elective procedures 1
• Pregnancy: Not recommended during pregnancy or in women who may become pregnant 1

When to Adjust the Protocol

• If severe gastrointestinal side effects occur, maintain the current dose for an additional 4 weeks before attempting to increase
• If side effects persist but benefits outweigh risks, consider dose reduction rather than discontinuation
• If inadequate glycemic response at 10mg, increase to maximum dose of 15mg

Long-term Considerations

Sudden discontinuation of tirzepatide results in regain of 50-67% of weight loss within 1 year, so long-term therapy is recommended for sustained benefits 5.