What is the recommended dosing regimen for initiating and titrating Mounjaro (tirzepatide) therapy?

From the Guidelines

Mounjaro (tirzepatide) therapy should be initiated at a dose of 2.5 mg injected subcutaneously once weekly for the first 4 weeks, and then titrated to 5 mg, 7.5 mg, and up to a maximum of 15 mg once weekly, as needed and tolerated, with each dose level maintained for at least 4 weeks before considering an increase 1.

Key Considerations for Prescribing Mounjaro

• The initial dose of 2.5 mg is intended to help patients adjust to the medication and minimize gastrointestinal side effects, rather than for glycemic control.
• The dose can be increased in 2.5 mg increments every 4 weeks until reaching the maximum recommended dose of 15 mg once weekly, based on the patient's response and tolerance.
• Patients should administer Mounjaro on the same day each week, but if needed, the day of administration can be changed as long as the last dose was administered at least 3 days (72 hours) prior.
• The medication should be injected into the abdomen, thigh, or upper arm, and injection sites should be rotated with each dose.

Titration Schedule

• The typical titration schedule progresses from 2.5 mg to 5 mg, then to 7.5 mg, 10 mg, 12.5 mg, and finally 15 mg, with each dose level maintained for at least 4 weeks before considering an increase.
• This gradual titration approach allows the body to adapt to the medication, reducing the likelihood and severity of side effects such as nausea, vomiting, and diarrhea.

Important Pharmacokinetic Properties

• Mounjaro has a bioavailability of 80% and a volume of distribution of 24 liters, with a fraction bound to plasma protein of 10.3% and an elimination half-life of 5 days 1.
• The medication is metabolized, with no active metabolite, and no dose change is necessary for patients with mild to moderate renal impairment.

From the FDA Drug Label

2 DOSAGE AND ADMINISTRATION

2.1 Dosage The recommended starting dosage of MOUNJARO is 2.5 mg injected subcutaneously once weekly. Follow the dosage escalation below to reduce the risk of gastrointestinal adverse reactions [see Warnings and Precautions (5.6) and Adverse Reactions (6.1)]. The 2. 5 mg dosage is for treatment initiation and is not intended for glycemic control. After 4 weeks, increase the dosage to 5 mg injected subcutaneously once weekly. If additional glycemic control is needed, increase the dosage in 2. 5 mg increments after at least 4 weeks on the current dose. The maximum dosage of MOUNJARO is 15 mg injected subcutaneously once weekly.

To prescribe Mounjaro 7.5mg, initiate therapy with a dose of 2.5mg injected subcutaneously once weekly for 4 weeks. Then, titrate the dosage to 5mg, and if additional glycemic control is needed, increase the dosage in 2.5mg increments after at least 4 weeks on the current dose.

• The recommended dosing regimen for Mounjaro is as follows:
  • Start with 2.5mg/week for 4 weeks
  • Increase to 5mg/week for at least 4 weeks
  • Increase by 2.5mg increments every 4 weeks as needed, up to a maximum dose of 15mg/week
• Dose escalation should be done to reduce the risk of gastrointestinal adverse reactions 2

From the Research

Dosing Regimen for Mounjaro (Tirzepatide) Therapy

The recommended dosing regimen for initiating and titrating Mounjaro (tirzepatide) therapy is as follows:

• The initial dose of tirzepatide is 2.5 mg once weekly for 4 weeks, followed by an increase to 5 mg once weekly 3
• The dose can be further increased to 10 mg once weekly if additional glycemic control is needed 3
• The maximum recommended dose of tirzepatide is 15 mg once weekly 3

Titration and Maintenance

• Titration of tirzepatide should be done in a stepwise manner, with a minimum of 4 weeks between dose increases 3
• The maintenance dose of tirzepatide is the dose that achieves the desired level of glycemic control, which can be 5 mg, 10 mg, or 15 mg once weekly 3

Special Considerations

• No dose adjustment is required for patients with renal impairment, as tirzepatide exposure is similar across renal impairment groups and healthy subjects 4
• Tirzepatide has been shown to be effective and safe in patients with type 2 diabetes, with a favorable safety profile compared to placebo 3

Key Points

• Tirzepatide is a dual GIP and GLP-1 receptor agonist that has been shown to be effective in improving glycemic control and reducing body weight in patients with type 2 diabetes 5, 3
• The recommended dosing regimen for tirzepatide involves a stepwise titration to achieve the desired level of glycemic control 3
• Tirzepatide has a favorable safety profile, with the most common adverse events being mild to moderate gastrointestinal events 3