What is the recommended dosing for Retatrutide (generic name)?

Retatrutide Dosing Recommendations

The recommended dosing for retatrutide is a once-weekly subcutaneous injection starting at 2 mg and gradually escalating to a maintenance dose of 8-12 mg for optimal efficacy in weight management and metabolic improvement. 1, 2

Dosing Protocol

• Initial dosing: Start with 2 mg subcutaneously once weekly 2, 1
• Dose escalation: Gradually increase dose to minimize gastrointestinal side effects 1
  • Weeks 1-4: 2 mg once weekly
  • Weeks 5-8: 4 mg once weekly
  • Weeks 9-12: 8 mg once weekly
  • Weeks 13+: Maintenance dose of 8-12 mg once weekly based on tolerability and clinical response 2, 1

Efficacy by Dose

• 0.5 mg: Minimal efficacy with 3.19% weight reduction at 36 weeks 2
• 4 mg: Moderate efficacy with 7.92-10.37% weight reduction at 36 weeks 2
• 8 mg: Strong efficacy with 16.34-16.81% weight reduction at 36 weeks 2
• 12 mg: Maximum efficacy with 16.94% weight reduction at 36 weeks 2
• Long-term results (48 weeks): Weight reductions of 22.8% and 24.2% with 8 mg and 12 mg doses, respectively 3

Clinical Considerations

• Glycemic control: Dose-dependent HbA1c reductions, with significant improvements at doses ≥4 mg 2

  • 8 mg dose: -1.99% HbA1c reduction at 24 weeks
  • 12 mg dose: -2.02% HbA1c reduction at 24 weeks 2

• Body composition effects: Significant reductions in total fat mass 4

  • 4 mg: 15.2% reduction in total fat mass
  • 8 mg: 26.1% reduction in total fat mass
  • 12 mg: 23.2% reduction in total fat mass 4

• Liver fat reduction: Dose-dependent effects at 24 weeks 3

  • 4 mg: 57.0% reduction
  • 8 mg: 81.4% reduction
  • 12 mg: 82.4% reduction 3

Adverse Effects Management

• Gastrointestinal effects: Most common adverse events (nausea, diarrhea, vomiting, constipation) 2, 1

  • Incidence increases with dose (13% at 0.5 mg to 50% at 8 mg) 2
  • Mostly mild to moderate in severity 1
  • Partially mitigated with lower starting dose and gradual titration 1

• Cardiovascular effects: Dose-dependent increases in heart rate 5, 1

  • Peak at 24 weeks and decline thereafter 1
  • Up to 6.7 beats/min increase 5

Special Populations

• Type 2 diabetes: Effective for both glycemic control and weight management 2
• Metabolic dysfunction-associated steatotic liver disease: Significant reductions in liver fat 3
• Obesity without diabetes: Substantial weight reductions over 48 weeks 1

Clinical Pearls

• Slower dose escalation (starting at 2 mg rather than 4 mg) improves gastrointestinal tolerability 1
• Weight loss continues beyond 24 weeks, with maximum benefits seen at 48 weeks 1
• No severe hypoglycemia reported in clinical trials 2
• Consider monitoring heart rate in patients with pre-existing cardiovascular conditions 5