What is the recommended dose and frequency of tirzepatide (glucagon-like peptide-1 (GLP-1) receptor agonist) for the treatment of type 2 diabetes?

Tirzepatide Dosing and Administration

Tirzepatide is administered as a once-weekly subcutaneous injection, starting at 2.5 mg weekly and titrating upward by 2.5 mg every 4 weeks until reaching the target maintenance dose of 5 mg, 10 mg, or 15 mg weekly. 1, 2

Standard Titration Schedule

The FDA-approved titration protocol follows a structured escalation to minimize gastrointestinal adverse effects while achieving therapeutic benefit:

• Weeks 1-4: Start at 2.5 mg subcutaneously once weekly 1
• Weeks 5-8: Increase to 5 mg once weekly 1
• Weeks 9-12: Increase to 7.5 mg once weekly (if targeting 10 mg or 15 mg maintenance dose) 1
• Weeks 13-16: Increase to 10 mg once weekly (if targeting 10 mg or 15 mg maintenance dose) 1
• Weeks 17-20: Increase to 12.5 mg once weekly (if targeting 15 mg maintenance dose) 1
• Week 21+: Reach maintenance dose of 15 mg once weekly 1

The dose escalation occurs in 2.5 mg increments every 4 weeks, regardless of the target maintenance dose. 1

Maintenance Dosing Options

Three maintenance doses are available based on glycemic control needs and weight loss goals:

• 5 mg weekly: Achieves HbA1c reduction of 1.87-2.24% and weight loss of 5.4-6.2 kg 2, 3, 4
• 10 mg weekly: Achieves HbA1c reduction of 2.24-2.58% and weight loss of 7.5-9.5 kg 2, 3, 4
• 15 mg weekly: Achieves HbA1c reduction of 2.24-2.59% and weight loss of 10.2-12.9 kg 2, 3, 4

For maximum weight loss and glycemic control, the 15 mg weekly dose demonstrates superior efficacy, with 20.9% total body weight loss at 72 weeks and 23.0-62.4% of patients achieving HbA1c <5.7% (normoglycemia). 5, 2, 4

Frequency and Route

• Frequency: Once weekly administration 5, 1, 2
• Route: Subcutaneous injection 5, 1, 2
• Timing: Can be administered at any time of day, with or without meals 1

Dose Selection Algorithm

Choose the target maintenance dose based on these clinical priorities:

1. For type 2 diabetes with obesity requiring maximum glycemic control and weight loss: Target 15 mg weekly 5, 2
2. For type 2 diabetes with moderate glycemic control needs: Target 10 mg weekly 2, 3
3. For patients with significant gastrointestinal intolerance or elderly patients: Consider maintaining at 5 mg weekly 1, 3

Missed Dose Management

• If 1 dose is missed: Administer as soon as possible within 4 days (96 hours) of the missed dose 1
• If more than 4 days have passed: Skip the missed dose and resume at the next regularly scheduled dose 1
• If 2 consecutive doses are missed: Resume at the same dose if previously well-tolerated 5
• If 3 or more consecutive doses are missed: Consider restarting the titration schedule from 2.5 mg weekly 5

Common Pitfalls to Avoid

• Do not escalate doses faster than every 4 weeks, as this significantly increases gastrointestinal adverse events (nausea, vomiting, diarrhea) 1, 2, 4
• Do not combine tirzepatide with other GLP-1 receptor agonists or DPP-4 inhibitors, as this creates pharmacologic redundancy and potential harm 5
• Do not use tirzepatide in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (absolute contraindication) 5, 3
• When combining with insulin or insulin secretagogues, reduce insulin by 20% at initiation to prevent hypoglycemia 5

Monitoring During Titration

• Weeks 0-16 (titration phase): Assess every 4 weeks for gastrointestinal tolerance, weight loss progress, and blood pressure 5
• After week 16 (maintenance phase): Monitor every 3 months minimum for weight, blood pressure, cardiovascular risk factors, and medication adherence 5
• Evaluate treatment efficacy at 12-16 weeks on maximum tolerated dose: If <5% weight loss achieved, consider treatment intensification or alternative approaches 5