What is the standard dosing for retatrutide (glucagon-like peptide-1 (GLP-1) receptor agonist)?

Standard Dosing for Retatrutide

Retatrutide is a novel triple hormone receptor agonist (glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptor) with a recommended dosing schedule that begins with a lower dose and gradually increases to minimize gastrointestinal side effects.

Recommended Dosing Schedule

• Initial dose should be 2 mg subcutaneously once weekly, with gradual dose escalation to minimize gastrointestinal side effects 1
• Dose titration should follow this schedule:
  • Start with 2 mg once weekly 1, 2
  • Increase by 2 mg increments every 4 weeks as tolerated 1
  • Target maintenance dose of 8-12 mg once weekly, based on efficacy and tolerability 1, 2

Dosing Considerations

• Lower starting dose (2 mg vs 4 mg) has been shown to partially mitigate gastrointestinal side effects 1
• Dose-dependent efficacy has been observed, with greater weight loss at higher maintenance doses 1, 2
• At 48 weeks in clinical trials:
  • 1 mg dose: 8.7% weight reduction
  • 4 mg dose: 17.1% weight reduction
  • 8 mg dose: 22.8% weight reduction
  • 12 mg dose: 24.2% weight reduction 1

Administration

• Administered as a subcutaneous injection once weekly 1, 2
• Similar administration method to other GLP-1 receptor agonists like semaglutide and dulaglutide 3

Monitoring and Adjustments

• Monitor for gastrointestinal side effects (nausea, vomiting, diarrhea) which are the most common adverse events 1, 2
• Assess weight loss response at regular intervals 1
• Consider dose adjustments based on:
  • Tolerability of side effects
  • Efficacy in terms of weight reduction
  • Patient-specific factors 1, 2

Special Considerations

• Dose-dependent increases in heart rate have been observed, peaking at 24 weeks and declining thereafter 1, 4
• Similar to other GLP-1 receptor agonists, retatrutide may require caution in patients with:
  • History of pancreatitis
  • Gastroparesis or delayed gastric emptying
  • History of medullary thyroid carcinoma 3

Efficacy Markers

• In clinical trials, retatrutide demonstrated significant reductions in:
  • Body weight (up to 24.2% at 12 mg dose) 1
  • Total body fat mass (up to 26.1% with 8 mg dose) 5
  • Liver fat (up to 82.4% with 12 mg dose) 6
  • HbA1c in patients with type 2 diabetes 2

Common Side Effects

• Gastrointestinal effects (dose-related):
  • Nausea
  • Diarrhea
  • Vomiting
  • Constipation 1, 2
• Increased heart rate (up to 6.7 beats/min) 4

Remember that retatrutide is a relatively new medication, and dosing recommendations may evolve as more clinical experience is gained with this agent.