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Retatrutide

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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
      • 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%

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