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These observations were supported by our mutagenesis studies, where mutations R299 ECL2 A in GLP-1R, R289 ECL2 A in GIPR and I194 2.67b K in GCGR caused variable decreases in retatrutide potency (by 3.7-fold, 4.6-fold and 36.0-fold, respectively), while S297 ECL2 A in GCGR slightly increased retatrutide potency

Researchers planning experiments should choose the diluent volume based on which component's working concentration anchors the experimental design

IGF-1 LR3 itself is not FDA-approved for general muscle growth or anti-aging use

3.2 Quality Assessment The risk of bias for the included trials is presented in Supplementary Figure S1