How to re-titrate a 52-year-old female on Zepbound (tirzepatide), a glucagon-like peptide-1 (GLP-1) receptor agonist, after a 1-month hiatus due to surgery?

From the Guidelines

For a 52-year-old female who has been off Zepbound (tirzepatide) 15 mg for one month due to surgery, I recommend restarting at a lower dose and gradually titrating back up to minimize gastrointestinal side effects, as suggested by the AGA clinical practice guideline on pharmacological interventions for adults with obesity 1. To achieve this, begin with 2.5 mg weekly for 4 weeks, then increase to 5 mg weekly for 4 weeks, followed by 7.5 mg weekly for 4 weeks, then 10 mg weekly for 4 weeks, and finally return to the 15 mg dose.

• This gradual approach is necessary because GLP-1 receptor agonist tolerance is lost after extended breaks, and restarting at the same dose can increase the risk of gastrointestinal side effects.
• The KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease also supports starting with a low dose of GLP-1 RA and titrating up slowly to minimize gastrointestinal side effects 1.
• Monitor for side effects like nausea, vomiting, or diarrhea during the titration period, and ensure adequate hydration.
• Consider taking anti-nausea medication if needed, and if severe side effects occur at any dose, remain at that dose for an additional week before attempting to increase again.
• This cautious re-titration helps rebuild tolerance to the medication while minimizing discomfort, as rapid reintroduction at the previous high dose could cause significant gastrointestinal distress that might lead to discontinuation.

From the FDA Drug Label

2.3 Recommendations Regarding Missed Dose If a dose is missed, instruct patients to administer ZEPBOUND as soon as possible within 4 days (96 hours) 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. In each case, patients can then resume their regular once weekly dosing schedule

The patient has been off ZEPBOUND for 1 month due to surgery. Re-titration is not explicitly addressed in the label for a patient who has been off the medication for an extended period. However, considering the patient was previously on 15 mg, it may be prudent to restart at a lower dose and titrate back up to minimize potential gastrointestinal adverse reactions, but this is not directly supported by the label. Given the lack of direct guidance, it is recommended to consult with the healthcare provider for personalized advice on re-titration. 2

From the Research

Re-titration of GLP-1 Medications After Discontinuation

To re-titrate a 52-year-old female patient on 15 mg injectable GLP-1 (Zepbound) after being off medications for 1 month due to surgery, consider the following steps:

• The patient was previously on a stable dose of GLP-1 medication, which was discontinued due to surgery 3.
• GLP-1 receptor agonists, such as Zepbound, have been shown to be effective in improving glycemic control and reducing body weight in patients with type 2 diabetes 4, 5.
• When re-initiating GLP-1 medication after a period of discontinuation, it is essential to consider the patient's current glycemic control and potential changes in their medical condition 6.
• The re-titration process may involve restarting the medication at a lower dose and gradually increasing it to the previous maintenance dose, monitoring the patient's response and adjusting the dose as needed 7.

Considerations for Re-titration

Some key considerations for re-titration include:

• The patient's current glycemic control and any changes in their medical condition, such as kidney function or cardiovascular risk factors 3, 7.
• The potential for gastrointestinal adverse effects, such as nausea and vomiting, which are common with GLP-1 receptor agonists 4, 5.
• The need for ongoing monitoring of the patient's response to the medication, including their glycemic control, weight, and potential adverse effects 6.
• The importance of patient education and support to ensure adherence to the medication regimen and to address any concerns or questions the patient may have 3, 7.