Retatrutide Dose Escalation Protocol
When starting with 10 units (2mg) of Retatrutide on a U-100 syringe, the recommended weekly dose increase is 5 units (1mg) every 4 weeks until reaching the target or maximum dose.
Dosing Schedule for Retatrutide
Retatrutide is a triple-hormone-receptor agonist that targets GIP, GLP-1, and glucagon receptors. When using a U-100 insulin syringe for administration, follow this structured titration protocol:
- Starting dose: 10 units (2mg) once weekly
- Dose escalation: Increase by 5 units (1mg) every 4 weeks
- Maintenance doses: Progress through 15 units (3mg), 20 units (4mg), up to maximum 24 units (4.8mg)
Evidence-Based Titration Protocol
The dose escalation protocol is based on clinical trial data showing that gradual titration helps mitigate gastrointestinal side effects while maintaining efficacy 1. The phase 2 trial of retatrutide demonstrated that:
- Slower titration (starting at 2mg rather than 4mg) resulted in fewer gastrointestinal adverse events
- Each dose increase should occur after an adequate trial period to assess response and tolerability
- A 4-week interval between dose increases allows for appropriate assessment of glycemic response and side effect profile
Monitoring During Dose Escalation
During the dose escalation period, monitor for:
- Gastrointestinal symptoms (nausea, vomiting, diarrhea) - the most common adverse events
- Changes in heart rate - dose-dependent increases may occur, typically peaking at 24 weeks 1
- Glycemic response - assess adequacy of current dose before escalating
Important Clinical Considerations
- Do not use with other GLP-1 receptor agonists or DPP-4 inhibitors
- If the patient is on insulin or sulfonylureas, monitor closely for hypoglycemia as dose adjustments of those medications may be needed
- Administer subcutaneously once weekly, with site rotation between abdomen, thigh, or upper arm
Practical Application
- Week 1-4: 10 units (2mg) once weekly
- Week 5-8: 15 units (3mg) once weekly
- Week 9-12: 20 units (4mg) once weekly
- Week 13+: Up to 24 units (4.8mg) once weekly if needed
This gradual titration approach optimizes the balance between efficacy and tolerability, as demonstrated in clinical trials showing substantial weight reduction (17-24% at higher doses) while minimizing adverse effects 1.