Retatrutide (LY3437943) is a next-generation synthetic peptide that simultaneously activates not two but three different hormone receptors: GIP, GLP-1 and the glucagon receptor. This triple receptor modulation represents the most complex mechanism of action in GLP-1-based research to date.
The Phase 2 TRIUMPH trial, published in 2023 in the New England Journal of Medicine by Jastreboff et al., showed a mean body weight reduction of 24.2 % with the highest dose (12 mg weekly) after 48 weeks in participants with obesity.
The key difference from tirzepatide is the additional glucagon receptor activation. Glucagon typically stimulates hepatic glucose release and increases energy expenditure (thermogenesis). In combination with GLP-1 and GIP, this blood-glucose-raising effect is largely offset while the metabolic fat-burning effect is preserved.
Preclinical data show that the glucagon component particularly enhances the reduction of visceral fat and hepatic steatosis (fatty liver). This could make retatrutide especially relevant for research into metabolically associated fatty liver disease.
Retatrutide is currently in Phase 3 development at Eli Lilly. In addition to the primary endpoint of body weight, the TRIUMPH Phase 2 programme also demonstrated positive effects on blood pressure, triglycerides and fasting glucose. The compound is not yet approved and is exclusively available for authorised scientific research. Studien Peptide provides retatrutide as a lyophilised peptide.
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