Initial Dosing of Tirzepatide (Mounjaro) When Switching from Semaglutide (Ozempic) 2 mg Weekly
When switching from Ozempic (semaglutide) 2 mg weekly to Mounjaro (tirzepatide), patients should start with the initial dose of 2.5 mg once weekly for 4 weeks, regardless of their previous semaglutide dose.
Recommended Dosing Schedule
- The recommended starting dosage of Mounjaro is 2.5 mg injected subcutaneously once weekly 1
- The 2.5 mg dosage is specifically intended for treatment initiation and is not intended for glycemic control 1
- After 4 weeks on the 2.5 mg dose, increase to 5 mg once weekly 1
- Further dose increases can be made in 2.5 mg increments after at least 4 weeks on the current dose 1
- The maximum dosage of Mounjaro is 15 mg injected subcutaneously once weekly 1
Rationale for Gradual Titration
- Gradual dose titration is essential to minimize gastrointestinal adverse effects, which are common with GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists 2
- Tirzepatide has a different mechanism of action than semaglutide, acting as a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist 2
- Even though patients may have developed tolerance to semaglutide's GI effects, tirzepatide's dual mechanism may cause new or different GI side effects 2
Administration Guidelines
- Mounjaro can be administered any time of day, with or without meals 1
- Inject subcutaneously in the abdomen, thigh, or upper arm 1
- Rotate injection sites with each dose 1
- If a dose is missed, administer as soon as possible within 4 days (96 hours) after the missed dose 1
- If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day 1
Common Side Effects and Management
- Gastrointestinal side effects are common with both medications but may be more pronounced with tirzepatide 2, 3, 4
- Common GI side effects include nausea, vomiting, diarrhea, and esophageal reflux 2
- Other potential side effects include injection site reactions and elevated heart rate 2
- Tirzepatide may delay gastric emptying, which could affect the absorption of oral medications 2
- Monitor for potential consequences of delayed absorption of oral medications, particularly those with narrow therapeutic indices 2
Efficacy Considerations
- Tirzepatide has demonstrated superior efficacy in weight reduction and glycemic control compared to semaglutide in clinical trials 3, 5, 4
- At maximum doses, tirzepatide 15 mg weekly has shown weight loss of 14.7% compared to 9.6% with semaglutide 2.4 mg weekly 2
- In patients with type 2 diabetes, tirzepatide has demonstrated greater reductions in HbA1c compared to semaglutide 3, 4
Special Considerations and Precautions
- Both medications carry a black box warning regarding the risk of thyroid C-cell tumors in rodents (human relevance not determined) 2
- Do not use in individuals with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 2
- Use caution in patients with kidney disease when initiating or increasing dose due to potential risk of acute kidney injury 2
- Advise females using oral contraceptives to switch to a non-oral contraception method or add a non-oral method for 4 weeks after initiation and for 4 weeks after each dose escalation 2
Monitoring Recommendations
- Assess efficacy and safety at least monthly for the first 3 months and at least quarterly thereafter 2
- Early responders (typically defined as >5% weight loss after 3 months' use) tend to have improved long-term outcomes 2
- Monitor for gastrointestinal disorders including severe constipation and small-bowel obstruction/ileus progression 2
- Be alert for potential cholelithiasis and gallstone-related complications 2
Remember that while patients may have been on a high dose of semaglutide (2 mg weekly), they must still start with the lowest dose of tirzepatide (2.5 mg weekly) to minimize adverse effects and ensure proper tolerance of this medication with a different mechanism of action.