Retatrutide

Retatrutide (LY3437943)

• is a single agent tri-agonist at the glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon (GCG) receptors
  
  
• retatrutide in obesity
  • in a phase 2 study at the 12-mg dose of retatrutide, more than 9 of 10 participants lost 10% or more of their baseline weight, nearly two thirds lost 20% or more, nearly half lost 25% or more, and a quarter lost 30% or more (1)
    
    
  • mean percentage change in body weight at 24 weeks (primary endpoint) was -7.2% in the retatrutide 1-mg group (n=69), -12.9% in the combined retatrutide 4-mg group (n=67), -17.3% in the combined retatrutide 8-mg group (n=70), and -17.5% in the retatrutide 12-mg group (n=62), compared with -1.6% in the placebo group (n=70)
    
    
  • mean percentage change at 48 weeks (secondary endpoint) was -8.7% in the retatrutide 1-mg group, -17.1% in the combined retatrutide 4-mg group, -22.8% in the combined retatrutide 8-mg group, and -24.2% in the retatrutide 12-mg group, compared with -2.1% in the placebo group
    
    
  • transient, mostly mild-to-moderate gastrointestinal events were the most frequently reported adverse events, occurring primarily during dose escalation
    
    
• retatrutide for type 2 diabetes
  • in a phase 2 study in comparison to liraglutide 1.5mg (2):
    • HbA1c reductions with retatrutide were significantly greater (p<0.0001) than placebo in all but the 0.5 mg group and greater than 1.5 mg dulaglutide in the 8 mg slow escalation group (p=0.0019) and 12 mg escalation group (p=0.0002)
    • HbA1c reduction was 2.02% in the 12 mg escalation group
    • also dose-dependently reduced systolic and diastolic blood pressure and improved lipid measures, notably reducing non-HDL cholesterol concentrations, while decreasing triglycerides by up to 35%
  • TRANSCEND-T2D-1 study (3):
    • retatrutride in in people with type 2 diabetes and inadequate glycaemic control with diet and exercise
      • participants were randomly assigned (1:1:1:1) to receive retatrutide (4 mg, 9 mg, or 12 mg) or placebo by once-weekly subcutaneous injection
      • mean change from baseline in HbA_1c concentration was –1·69% (SE 0·11) with retatrutide 4 mg, –1·86% (0·10) with 9 mg, and –1·94% (0·08) with 12 mg, versus –0·81% (0·12) with placebo
      • mean percentage change from baseline in bodyweight was –11·5% (SE 0·7) with retatrutide 4 mg, –13·9% (0·8) with 9 mg, and –15·3% (0·8) with 12 mg, versus –2·6% (0·5) with placebo

Reference:

1. Jastreboff AM et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. NEJM June 26, 2023 DOI: 10.1056/NEJMoa2301972
2. Rosenstock J et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet June 26, 2023DOI:https://doi.org/10.1016/S0140-6736(23)01053-X
3. Bajaj H et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. The Lancet, 2026.