Preliminary Dosing Recommendations for Retatrutide
Based on the most recent clinical evidence, retatrutide should be administered as a once-weekly subcutaneous injection with a gradual dose escalation schedule starting at 2 mg and increasing to a target maintenance dose of 4-12 mg depending on efficacy and tolerability. 1
Initial Dosing and Escalation Schedule
- The recommended starting dose is 2 mg subcutaneously once weekly, which has been shown to improve tolerability compared to starting at higher doses 1
- After 4 weeks at the starting dose, the dose can be escalated to 4 mg once weekly 1, 2
- Further dose escalation can proceed in 4 mg increments (to 8 mg, then 12 mg) at 4-week intervals based on clinical response and tolerability 1
- The maximum recommended dose is 12 mg once weekly, which demonstrated the greatest weight reduction in clinical trials (24.2% at 48 weeks) 1
Administration Considerations
- Retatrutide should be administered subcutaneously in the abdomen, thigh, or upper arm 1
- The injection should be given on the same day each week, although the time of day and injection site can be changed if needed 1
- The medication can be administered with or without food 2
Efficacy Considerations
Dose-dependent weight reduction has been observed with retatrutide:
- 1 mg: 8.7% reduction at 48 weeks
- 4 mg: 17.1% reduction at 48 weeks
- 8 mg: 22.8% reduction at 48 weeks
- 12 mg: 24.2% reduction at 48 weeks 1
For patients with type 2 diabetes, retatrutide also demonstrates dose-dependent HbA1c reduction:
- 4 mg: 1.30-1.39% reduction
- 8 mg: 1.88-1.99% reduction
- 12 mg: 2.02% reduction 2
Monitoring and Follow-up
- Evaluate weight loss response after 12 weeks at the maintenance dose 1
- Consider dose escalation if a patient has not achieved at least 5% weight reduction at this timepoint 1
- Monitor for gastrointestinal side effects, which are the most common adverse events 1, 2
- Monitor heart rate, as dose-dependent increases have been observed (peaking at 24 weeks and declining thereafter) 1
Safety Considerations
- The most common adverse events are gastrointestinal in nature (nausea, diarrhea, vomiting, constipation) 1, 2
- These side effects are typically mild to moderate in severity and can be partially mitigated with the lower starting dose of 2 mg 1
- The incidence of gastrointestinal adverse events increases with higher doses:
- 0.5 mg: 13% of patients
- 8 mg: up to 50% of patients 2
- No severe hypoglycemia events were reported in clinical trials 2
Special Populations
- For patients with type 2 diabetes, retatrutide has shown significant improvements in both glycemic control and body weight 2
- Body composition studies show significant reductions in total fat mass with retatrutide compared to placebo:
- 4 mg: 15.2% reduction
- 8 mg: 26.1% reduction
- 12 mg: 23.2% reduction 3
Clinical Pearls
- The proportion of lean mass loss to weight loss with retatrutide is similar to other obesity treatments 3
- Retatrutide is a triple hormone receptor agonist that targets GIP, GLP-1, and glucagon receptors 4, 1
- The 12 mg dose has shown the greatest efficacy in clinical trials but also has the highest incidence of side effects 1, 5
- Using the recommended dose escalation schedule helps mitigate gastrointestinal side effects 1