What dose of Ozempic (semaglutide) should a patient restart with after missing 3 weeks of treatment, having previously been on 1 mg once weekly?

Restarting Ozempic After Missing 3 Weeks of Doses

For a patient who has missed 3 weeks of Ozempic (semaglutide) at a dose of 1 mg, the patient should restart at 0.5 mg weekly for 4 weeks before returning to the 1 mg dose.

Rationale for Dose Reduction

According to the American Gastroenterological Association's clinical practice guidelines, when 3 or more consecutive doses of a GLP-1 receptor agonist like semaglutide are missed, the titration schedule should be restarted 1. This recommendation is based on the following considerations:

• Missing multiple consecutive doses can lead to loss of gastrointestinal tolerance
• Restarting at the full 1 mg dose may cause significant adverse effects
• Gradual re-titration helps minimize gastrointestinal side effects

Recommended Re-titration Schedule

1. Week 1-4: Start with 0.5 mg once weekly for 4 weeks
2. Week 5 onwards: Return to the maintenance dose of 1 mg once weekly

This approach is supported by the FDA labeling for Ozempic, which emphasizes the importance of dose titration to minimize gastrointestinal adverse effects 2. While the FDA label specifically addresses what to do if a dose is missed within 5 days, clinical judgment is needed for longer periods of missed doses.

Considerations for Re-titration

The need for re-titration is based on several factors:

• Half-life considerations: Semaglutide has a half-life of approximately one week, so after 3 weeks (approximately 3 half-lives), plasma levels would be significantly reduced
• GI tolerance: Restarting at the full dose may cause unnecessary gastrointestinal side effects including nausea, vomiting, and diarrhea
• Patient comfort: A gradual re-titration improves tolerability and adherence

Common Pitfalls to Avoid

1. Restarting at the full 1 mg dose: This may cause severe gastrointestinal side effects and potentially lead to treatment discontinuation
2. Restarting at the lowest initiation dose (0.25 mg): This is unnecessarily conservative for a patient who previously tolerated 1 mg and would delay return to effective treatment
3. Skipping the re-titration altogether: This increases the risk of adverse effects and may compromise adherence

Monitoring Recommendations

• Monitor for gastrointestinal side effects during re-titration
• Ensure the patient resumes the regular once-weekly dosing schedule
• Advise the patient that if a dose is missed in the future, they should take it as soon as possible within 5 days after the missed dose 2
• If more than 5 days have passed, they should skip the missed dose and administer the next dose on the regularly scheduled day

By following this approach, the patient can safely return to effective treatment while minimizing adverse effects and optimizing adherence to therapy.