Tirzepatide (Mounjaro) Dosing and Frequency
Tirzepatide (Mounjaro) should be administered as a once-weekly subcutaneous injection, starting at 2.5 mg and gradually titrating upward to minimize gastrointestinal side effects.
Initial Dosing and Titration Schedule
Tirzepatide (Mounjaro) is a novel dual glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist used for the management of type 2 diabetes mellitus 1, 2, 3. The recommended dosing schedule is:
- Starting dose: 2.5 mg subcutaneously once weekly for 4 weeks
- First titration: Increase to 5 mg once weekly for 4 weeks
- Second titration: Increase to 7.5 mg once weekly for 4 weeks
- Third titration: Increase to 10 mg once weekly for 4 weeks
- Fourth titration: Increase to 12.5 mg once weekly for 4 weeks
- Maintenance dose: 15 mg once weekly
This gradual titration approach is critical to minimize gastrointestinal adverse effects, which are the most common side effects associated with tirzepatide 3.
Administration
- Tirzepatide is available as single-dose prefilled pens and single-dose vials 3
- Administer subcutaneously in the abdomen, thigh, or upper arm
- Injection should be given on the same day each week, but the time of day can be changed if needed
- If a dose is missed, administer as soon as possible within 4 days after the missed dose; if more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day
Special Populations
Renal Impairment
- No dosage adjustment is required for mild to moderate renal impairment
- Use with caution in severe renal impairment or end-stage renal disease
Hepatic Impairment
- No dosage adjustment is required for mild to moderate hepatic impairment
- Limited data available for severe hepatic impairment
Monitoring and Safety Considerations
Gastrointestinal Effects
- Monitor for nausea, vomiting, diarrhea, and decreased appetite, especially during dose escalation 3
- These side effects are typically mild to moderate and tend to decrease over time
Hypoglycemia Risk
- Risk is low when used as monotherapy but increases when combined with insulin secretagogues or insulin
- Monitor blood glucose levels, especially when initiating therapy or adjusting doses
Pancreatitis Risk
- Rare but serious complication
- Discontinue tirzepatide if pancreatitis is suspected 4
- Patients should be informed about symptoms of pancreatitis (severe abdominal pain that may radiate to the back, with or without vomiting)
Clinical Efficacy
Tirzepatide has demonstrated superior glycemic control and weight loss compared to other GLP-1 receptor agonists in clinical trials:
- Superior to dulaglutide 0.75 mg and semaglutide 1 mg for glycemic control
- Significant weight reduction benefits
- Low risk of clinically significant hypoglycemia when used without insulin or insulin secretagogues 3
Important Precautions
- Switching from other GLP-1 agonists: Follow the titration schedule from the beginning when switching from another GLP-1 receptor agonist to tirzepatide to reduce the risk of adverse effects, including acute pancreatitis 4
- Pregnancy and lactation: Limited data available; use only if potential benefit justifies potential risk to the fetus
- Concurrent medications: Review for potential interactions, especially with medications that affect gastric emptying
By following this structured dosing approach and monitoring for potential adverse effects, tirzepatide can be effectively and safely used to improve glycemic control in patients with type 2 diabetes mellitus.