Retatrutide at a glance
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Retatrutide (LY3437943) is a once-weekly injectable triagonist developed by Eli Lilly that simultaneously activates three receptors: GIP, GLP-1, and glucagon. By adding glucagon receptor agonism to the dual GIP/GLP-1 mechanism of tirzepatide, retatrutide introduces thermogenesis - increased energy expenditure via glucagon's activation of brown adipose tissue - as a third mechanism of weight loss.
In the Phase 2 TRIUMPH-1 trial (2023), retatrutide produced mean body weight loss of 24.2% at the highest dose (12mg) over 48 weeks, with some participants losing up to 29%. This represents the largest weight reduction ever reported for a pharmacological intervention in clinical trials, exceeding both semaglutide (~15%) and tirzepatide (~22%) in comparable timeframes.
Phase 3 trials (TRIUMPH program) are actively enrolling. Retatrutide is not yet approved for any indication. Its glucagon component raises theoretical concerns about lean mass preservation, but trial data to date show favorable body composition changes, likely due to the concurrent GIP/GLP-1 activity and the trial's protein intake guidance.
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