What is the starting dose of Monjauro?

Tirzepatide (Mounjaro) Starting Dose

The recommended starting dose of tirzepatide (Mounjaro) is 2.5 mg administered subcutaneously once weekly for 4 weeks, followed by gradual dose escalation.

Dosing Schedule and Titration

Tirzepatide requires a specific dose titration schedule to minimize gastrointestinal side effects:

1. Initial dose: 2.5 mg once weekly for 4 weeks
2. Titration schedule:
   • After 4 weeks at 2.5 mg: increase to 5 mg once weekly
   • After 4 weeks at 5 mg: increase to 7.5 mg once weekly
   • After 4 weeks at 7.5 mg: increase to 10 mg once weekly
   • After 4 weeks at 10 mg: increase to 12.5 mg once weekly
   • After 4 weeks at 12.5 mg: increase to 15 mg once weekly (maximum dose)

Administration Guidelines

• Administer subcutaneously in the abdomen, thigh, or upper arm
• Can be administered any time of day, with or without meals
• Maintain consistent day of administration each week
• If a dose is missed, administer within 4 days of the missed dose; if more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day

Clinical Evidence

Tirzepatide is a first-in-class dual incretin agonist that acts on both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors 1. The starting dose of 2.5 mg is not intended to be therapeutic but serves as an introduction to minimize gastrointestinal side effects, which are the most common adverse reactions 2.

In phase III SURPASS trials, tirzepatide demonstrated superior glycemic control and weight loss compared to GLP-1 receptor agonists like dulaglutide and semaglutide, as well as basal and prandial insulin 1.

Important Considerations

Side Effect Management

• Gastrointestinal effects (nausea, diarrhea, decreased appetite, vomiting) are the most common adverse events 1
• These side effects are typically mild to moderate and decrease over time with continued treatment
• The slow dose escalation schedule is specifically designed to minimize these effects

Contraindications and Precautions

• Personal or family history of medullary thyroid carcinoma
• Multiple Endocrine Neoplasia syndrome type 2
• Prior serious hypersensitivity reaction to tirzepatide
• Use caution in patients with diabetic retinopathy, pancreatitis history, or severe gastrointestinal disease

Monitoring

• Monitor blood glucose regularly during initiation and dose titration
• Assess for signs of pancreatitis (persistent severe abdominal pain)
• Monitor for hypoglycemia, especially if used with insulin secretagogues or insulin

Clinical Pearls

• The low starting dose of 2.5 mg is critical for tolerability and should not be skipped
• Patients should be counseled that the starting dose is not expected to provide full glycemic benefit
• Dose escalation should proceed only if the current dose is well tolerated
• If a patient cannot tolerate a dose increase, consider maintaining the current dose for an additional 4 weeks before attempting escalation again

Tirzepatide has demonstrated potent glucose-lowering effects and significant weight reduction benefits, making the proper initiation with the 2.5 mg starting dose essential for treatment success and adherence.