What is the FDA approval status of Retatrutide?

FDA Approval Status of Retatrutide

Retatrutide is not currently FDA approved for any indication as of 2024. While other medications like resmetirom have received FDA approval for metabolic dysfunction-associated steatohepatitis (MASH), retatrutide remains in clinical development 1.

Current Status of Retatrutide

• Retatrutide is a novel triple-hormone receptor agonist that targets glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors 2
• It is currently being investigated in clinical trials for obesity and type 2 diabetes management 2, 3
• Phase 2 clinical trials have been completed, but the medication has not yet received FDA approval 2, 4
• The most recent research shows promising results for weight management, with participants in a phase 2 trial achieving 24.2% weight reduction at the highest dose (12mg) after 48 weeks 2

Clinical Trial Results

• In a phase 2 randomized controlled trial for obesity treatment, retatrutide demonstrated dose-dependent weight reduction:

  • 8.7% weight loss at 1mg dose
  • 17.1% weight loss at 4mg dose
  • 22.8% weight loss at 8mg dose
  • 24.2% weight loss at 12mg dose 2

• In patients with type 2 diabetes, retatrutide showed significant improvements in:

  • Glycemic control (HbA1c reductions up to 2.02% at 12mg dose)
  • Body weight (reductions up to 16.94% at 12mg dose)
  • Body composition (total fat mass reductions up to 26.1% at 8mg dose) 4, 3

Safety Profile

• The most common adverse events in clinical trials were gastrointestinal in nature:

  • Nausea, diarrhea, vomiting, and constipation 2, 3
  • These were generally mild to moderate in severity 2
  • Gastrointestinal side effects were partially mitigated with lower starting doses 2

• Dose-dependent increases in heart rate were observed, peaking at 24 weeks and declining thereafter 2

• Retatrutide has demonstrated inotropic effects in isolated human atrial preparations, suggesting potential cardiac effects that warrant monitoring 5

Comparison to FDA-Approved Medications

• Unlike resmetirom, which received FDA conditional approval on March 14,2024, for fibrotic MASH (stage 2 or 3) 1, retatrutide has not yet received regulatory approval
• Several other medications have received FDA approval for metabolic conditions:
  • Selpercatinib and pralsetinib for RET-altered solid tumors 1
  • Larotrectinib and entrectinib for NTRK gene fusion-positive solid tumors 1

Future Prospects

• Retatrutide is currently in clinical development with ongoing trials
• Based on the promising phase 2 results, phase 3 trials are being planned or conducted 3
• A systematic review and meta-analysis of randomized controlled trials has confirmed significant improvements in body weight and metabolic outcomes with retatrutide, supporting its potential future approval 6

While retatrutide shows promise as a weight management and metabolic treatment option, healthcare providers should be aware that it remains investigational and is not yet available for clinical use outside of research settings.