Retatrutide Administration Guidelines
Retatrutide should be administered as a once-weekly subcutaneous injection, starting with a lower initial dose of 2 mg and gradually increasing to minimize gastrointestinal side effects. 1, 2
Dosing Schedule
- Retatrutide is administered as a once-weekly subcutaneous injection, supported by its approximately 6-day half-life 3
- A dose titration approach is recommended to improve tolerability 1, 2:
- Begin with 2 mg once weekly for initial dosing
- Gradually increase to target maintenance dose (4 mg, 8 mg, or 12 mg) based on clinical response and tolerability
- Slower titration (starting with 2 mg vs 4 mg) helps mitigate gastrointestinal side effects 1
Administration Technique
- Administer subcutaneously in the abdomen, thigh, or upper arm 1, 2
- Injection can be given at any time of day, with or without meals 2
- Maintain consistent day of the week for administration to establish routine 2
- If a dose is missed, administer as soon as possible if within 4 days of scheduled dose; otherwise, skip the missed dose and resume regular schedule 3
Dose Escalation Protocol
- Week 1-4: 2 mg once weekly (initial dose)
- Week 5-8: 4 mg once weekly (if tolerated)
- Week 9-12: 8 mg once weekly (if tolerated and clinically indicated)
- Week 13 and beyond: Up to 12 mg once weekly (if needed for optimal response) 1, 2
Special Considerations
- Gastrointestinal disorders (nausea, diarrhea, vomiting, constipation) are the most common adverse effects, typically mild to moderate in severity 2, 3
- Slower dose escalation significantly improves tolerability, particularly for higher doses 1
- Monitor for changes in heart rate, which may increase dose-dependently, typically peaking at 24 weeks and declining thereafter 1
- No dose adjustment appears necessary for patients with mild to moderate renal impairment, though data in severe renal impairment is limited 2
Clinical Efficacy Context
- Retatrutide is a triple agonist targeting glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor, and glucagon receptor 3
- Clinical trials have demonstrated significant weight reduction (8.7% at 1 mg, 17.1% at 4 mg, 22.8% at 8 mg, and 24.2% at 12 mg after 48 weeks) 1
- In patients with type 2 diabetes, retatrutide showed clinically meaningful improvements in glycemic control alongside robust weight reduction 2
- Significant reductions in total body fat mass have been observed with retatrutide treatment compared to placebo and dulaglutide 4
Common Pitfalls to Avoid
- Starting with too high a dose increases risk of gastrointestinal side effects 1, 2
- Inconsistent administration timing may affect efficacy and tolerability 3
- Failure to counsel patients about expected gastrointestinal side effects may lead to unnecessary discontinuation 2, 3
- Not monitoring for potential increases in heart rate, especially during the first 24 weeks of treatment 1