What is the recommended titration schedule for Zepbound (tirzepatide)?

Tirzepatide (Zepbound) Titration Schedule

The recommended titration schedule for Zepbound (tirzepatide) is to start at 2.5 mg once weekly for 4 weeks, then increase by 2.5 mg every 4 weeks until the target maintenance dose (5 mg, 10 mg, or 15 mg) is reached. 1

Initial Dosing and Escalation Protocol

• Start with 2.5 mg subcutaneously once weekly for the first 4 weeks 1
• Increase to 5 mg once weekly for weeks 5-8 1
• For patients targeting the 10 mg dose:
  • Increase to 7.5 mg once weekly for weeks 9-12 1
  • Increase to 10 mg once weekly for week 13 and beyond 1
• For patients targeting the 15 mg dose:
  • Increase to 7.5 mg once weekly for weeks 9-12 1
  • Increase to 10 mg once weekly for weeks 13-16 1
  • Increase to 12.5 mg once weekly for weeks 17-20 1
  • Increase to 15 mg once weekly for week 21 and beyond 1

Dose Selection Considerations

• The maximum recommended maintenance dose is 15 mg once weekly, which provides the greatest weight loss benefit (14.7% reduction from baseline) 1, 2
• The 10 mg dose provides substantial efficacy (12.8% weight reduction) and may be appropriate for those who cannot tolerate the 15 mg dose 1, 2
• The 5 mg dose is the minimum effective maintenance dose (10% weight reduction) 1

Managing Dose Escalation Side Effects

• Gastrointestinal side effects (nausea, vomiting, diarrhea) are most common during dose escalation 1, 2
• If patients experience intolerable gastrointestinal effects, consider:
  • Maintaining the current dose for an additional 4 weeks before attempting further escalation 1, 2
  • Reducing food intake and focusing on smaller, more frequent meals 1, 3
  • Avoiding high-fat meals around the time of injection 1, 2

Special Considerations

• For patients with renal impairment, use caution when initiating or increasing the dose due to potential risk of acute kidney injury 1
• Monitor for potential consequences of delayed gastric emptying, particularly in the perioperative setting 1
• For patients using oral contraceptives, advise switching to a non-oral method or adding a non-oral method for 4 weeks after initiation and for 4 weeks after each dose escalation 1
• Monitor oral medications with narrow therapeutic indices (e.g., warfarin) or medications whose efficacy depends on threshold concentrations 1

Clinical Pearls

• The gradual titration schedule is designed to improve gastrointestinal tolerability 1, 2
• Most gastrointestinal side effects are mild to moderate and occur primarily during dose escalation 2, 3
• Less than 5% of patients discontinue treatment due to adverse events 2
• The full weight loss effect may take several months to achieve, with continued benefits observed through 72 weeks of treatment 2, 3
• Tirzepatide demonstrates superior weight loss compared to GLP-1 receptor agonists like semaglutide and liraglutide 1, 4

Monitoring During Titration

• Assess tolerability before each dose escalation 1, 2
• Monitor for signs of pancreatitis (although causality has not been established) 1
• Watch for potential gallbladder-related complications 1
• Be alert for severe gastrointestinal disorders including constipation and small bowel obstruction/ileus progression 1

By following this structured titration approach, patients are more likely to achieve optimal therapeutic benefits while minimizing adverse effects associated with tirzepatide therapy.