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They do this by binding to and activating the GLP-1 receptor to cause the same effect as natural GLP-1
In a Phase 2 randomised controlled trial published in the New England Journal of Medicine in 2023 (Jastreboff et al., NEJM 2023), adults with obesity (without type 2 diabetes) who received the highest dose of retatrutide (12 mg weekly) achieved a mean body weight reduction of approximately 24% over 48 weeks
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The dose-response relationship of peptides can be incredibly sensitive
Both endogenous and synthetic GLP-1, as well as a GLP-1R antagonist, exendin 939, reduced heat sensitivity in nave mice