Retatrutide

Overview

Retatrutide is Eli Lilly's investigational triple-agonist research compound currently in Phase 3 trials. It activates three metabolic receptors simultaneously — GLP-1, GIP, and glucagon — and has produced the largest mean weight reduction of any research compound in published clinical data to date.

Mechanism of action

GLP-1 activation drives insulin secretion and satiety. GIP activation improves insulin sensitivity and fat utilisation. Glucagon receptor activation, the novel third arm, increases basal energy expenditure. The combined effect is greater appetite suppression and fat oxidation than dual agonists.

Reference range (research literature)

Phase 2 trials titrated from 0.5mg to 12mg weekly via subcutaneous injection. Research protocols commonly start at 2mg/week and titrate upward by 2mg every 4 weeks based on tolerability.

Half-life

Approximately 6 days — supports once-weekly dosing.

Reconstitution

Reconstitute the 10mg vial with 2ml bacteriostatic water. Each 0.2ml on a U100 syringe = 1mg. Refrigerate after reconstitution and use within 30 days.

Comparisons

• vs Tirzepatide

  Tirzepatide is dual GLP-1/GIP. Retatrutide adds glucagon for greater energy expenditure.

• vs Semaglutide

  Semaglutide is GLP-1 only. Retatrutide showed roughly 2x the weight reduction in head-to-head comparisons.

Commonly researched stacks

• Tesamorelin (GH/IGF-1 axis)
• MOTS-C (mitochondrial support)

Frequently asked