How quickly should I titrate tirzepatide (Mounjaro)?

Tirzepatide (Zepbound) Titration Schedule

The initial titration for tirzepatide begins at 2.5mg weekly for 4 weeks before increasing to the 5mg maintenance dose, with further titration to 7.5mg, 10mg, 12.5mg, and a maximum of 15mg once weekly as tolerated, with each dose increase occurring at 4-week intervals. 1

Standard Titration Schedule

Tirzepatide should be titrated gradually to minimize gastrointestinal side effects:

1. Start with 2.5mg once weekly for 4 weeks
2. Increase to 5mg once weekly for 4 weeks
3. Increase to 7.5mg once weekly for 4 weeks
4. Increase to 10mg once weekly for 4 weeks
5. Increase to 12.5mg once weekly for 4 weeks
6. Increase to maximum dose of 15mg once weekly

Administration Guidelines

• Administer subcutaneously in the abdomen, thigh, or upper arm
• Rotate injection sites with each dose
• Can be administered at any time of day, with or without meals 1
• No dosage adjustments are required for patients with renal impairment 1

Monitoring During Titration

• Monthly assessment during the first 3 months of therapy, then quarterly thereafter 1
• Evaluate for gastrointestinal side effects (nausea, vomiting, diarrhea, constipation)
• Assess weight loss progress - achieving >5% weight loss after 3 months typically predicts better long-term outcomes 1

Managing Side Effects During Titration

The most common adverse effects during titration are gastrointestinal:

• Nausea (31%)
• Diarrhea (23%)
• Vomiting (12%)
• Constipation (5%) 1

Side Effect Management Strategies:

• Start at the recommended low dose (2.5mg)
• Titrate slowly according to the schedule
• Reduce meal size
• Avoid high-fat foods
• Limit alcohol and carbonated drinks 1

Important Considerations

• If a patient experiences significant gastrointestinal side effects, consider extending the time at the current dose before increasing
• Do not accelerate the titration schedule beyond the recommended 4-week intervals
• Patients using oral hormonal contraception should use or add a non-oral method for 4 weeks after initiation and after each dose escalation 1
• Discontinuation of therapy leads to regaining one-half to two-thirds of lost weight within a year, emphasizing the importance of continued therapy 1

Clinical Efficacy

Tirzepatide has demonstrated substantial weight loss in clinical trials:

• Mean reduction of 20.9% from baseline compared to 3.1% with placebo in adults with obesity 2
• Superior weight reduction compared to semaglutide (additional 1.9-5.5kg weight loss) 3

Following this titration schedule optimizes both efficacy and tolerability, allowing patients to achieve maximum therapeutic benefit while minimizing adverse effects.