What is the recommended dose of tirzapatide (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist) for the treatment of type 2 diabetes?

Tirzepatide Dosing for Type 2 Diabetes

Start tirzepatide at 2.5 mg subcutaneously once weekly for 4 weeks, then escalate to 5 mg once weekly, with further increases to 10 mg or 15 mg (maximum dose) in 2.5 mg increments every 4 weeks based on glycemic response. 1, 2

Dose Initiation

• Begin with 2.5 mg subcutaneously once weekly for the first 4 weeks 1, 2
• The 2.5 mg dose is for treatment initiation only and is not an approved maintenance dose 2
• This gradual initiation reduces gastrointestinal adverse reactions (nausea, vomiting, diarrhea) which are the most common side effects 3, 2

Dose Escalation Algorithm

After the initial 4-week period at 2.5 mg:

• Week 5 onward: Increase to 5 mg once weekly 1, 2
• If additional glycemic control needed: After at least 4 weeks on 5 mg, escalate to 10 mg once weekly 1
• If further glycemic control needed: After at least 4 weeks on 10 mg, escalate to 15 mg once weekly (maximum dose) 1, 2

Maintenance Dosing

• Standard maintenance doses: 5 mg, 10 mg, or 15 mg once weekly 1, 2
• Maximum dose: 15 mg once weekly 1, 2
• The 10 mg dose produces approximately 12.8% weight loss from baseline 1
• The 15 mg dose achieves approximately 14.7% weight loss from baseline 1

Expected Glycemic Outcomes by Dose

Based on the SURPASS trials:

• 5 mg weekly: HbA1c reduction of approximately 2.11% from baseline 4
• 10 mg weekly: HbA1c reduction of approximately 2.40% from baseline 4
• 15 mg weekly: HbA1c reduction of approximately 2.34% from baseline 4
• Between 85-90% of patients achieve HbA1c <7% across all maintenance doses 4

Administration Details

• Inject subcutaneously in the abdomen, thigh, or upper arm 2
• Administer once weekly at any time of day, with or without meals 2
• Rotate injection sites with each dose 2
• If a dose is missed, administer within 4 days (96 hours); if more than 4 days have passed, skip and resume regular schedule 2

Critical Safety Considerations When Dosing

When adding tirzepatide to existing insulin therapy: Reassess and reduce insulin dosing to minimize hypoglycemia risk, as tirzepatide significantly reduces severe hypoglycemia compared to insulin (RR 0.21, CI 0.11-0.38) 1, 3

Dose adjustment for tolerability: If patients do not tolerate a maintenance dose, consider stepping back to a lower maintenance dose rather than discontinuing 2

Contraindications to any dose:

• Personal or family history of medullary thyroid carcinoma (MTC) 2
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 2
• Known serious hypersensitivity to tirzepatide 2

Common Pitfalls to Avoid

• Do not skip the 2.5 mg initiation phase - this significantly increases gastrointestinal side effects 2
• Do not escalate doses faster than every 4 weeks - premature escalation increases adverse events and discontinuation rates 2
• Do not combine with other GLP-1 receptor agonists - tirzepatide contains dual GIP/GLP-1 activity and should not be coadministered with other GLP-1 agonists 2
• Exercise caution in kidney disease - when initiating or increasing doses due to potential risk of acute kidney injury 3