What is the recommended dose of retatrutide?

Recommended Dosing of Retatrutide

The recommended dosing for retatrutide begins at 2 mg once weekly by subcutaneous injection, with gradual dose escalation to a maintenance dose of 4-12 mg weekly, with 8-12 mg showing the most significant clinical benefits for weight reduction. 1

Dosing Protocol and Escalation

• Initial starting dose should be 2 mg administered subcutaneously once weekly, which has been shown to improve tolerability compared to starting at higher doses 1
• Dose should be gradually increased following this schedule:
  • Start with 2 mg once weekly for initial titration period 1
  • Gradually increase to maintenance dose of 4 mg, 8 mg, or 12 mg once weekly based on clinical response and tolerability 1, 2
• The 8 mg and 12 mg doses have demonstrated the greatest efficacy for weight reduction in clinical trials, with 24.2% weight reduction at 48 weeks with the 12 mg dose 1

Efficacy by Dose

• 1 mg weekly: Produces modest weight reduction of approximately 8.7% at 48 weeks 1
• 4 mg weekly: Results in approximately 17.1% weight reduction at 48 weeks 1
• 8 mg weekly: Achieves approximately 22.8% weight reduction at 48 weeks 1
• 12 mg weekly: Provides the greatest weight reduction at approximately 24.2% at 48 weeks 1

Administration Considerations

• Retatrutide should be administered subcutaneously once weekly 1, 3
• Therapeutic response is dose-dependent, with higher doses providing greater efficacy for weight reduction 1, 2
• Lower starting doses (2 mg) with gradual escalation help mitigate gastrointestinal side effects compared to starting at higher doses (4 mg) 1

Monitoring and Expected Outcomes

• At 48 weeks, weight reduction of ≥5% occurs in:
  • 92% of patients receiving 4 mg weekly 1
  • 100% of patients receiving 8 mg weekly 1
  • 100% of patients receiving 12 mg weekly 1
• Weight reduction of ≥15% occurs in:
  • 60% of patients receiving 4 mg weekly 1
  • 75% of patients receiving 8 mg weekly 1
  • 83% of patients receiving 12 mg weekly 1

Common Side Effects and Management

• Gastrointestinal effects are the most common adverse events and are dose-related 1, 4, 3
  • Nausea, diarrhea, and vomiting are most frequently reported 4, 3
  • These side effects are typically mild to moderate in severity 1, 3
• Dose-dependent increases in heart rate may occur, peaking at approximately 24 weeks and declining thereafter 1, 4
  • Heart rate increases up to 6.7 beats per minute have been reported 4

Additional Clinical Benefits

• Beyond weight reduction, retatrutide demonstrates:
  • Significant reductions in total body fat mass (up to 26.1% with 8 mg dose) 2
  • Improvements in glycemic control in patients with type 2 diabetes 3
  • Substantial reductions in liver fat in patients with metabolic dysfunction-associated steatotic liver disease (up to 82.4% with 12 mg dose) 5

Clinical Pitfalls to Avoid

• Starting at higher doses (4 mg) rather than the recommended 2 mg may increase the risk and severity of gastrointestinal side effects 1
• Failure to gradually escalate the dose may lead to poor tolerability and potential discontinuation 1, 3
• Patients should be monitored for cardiovascular effects, particularly increased heart rate, which may offset some benefits of weight loss 4