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Combining CagriSema (which contains semaglutide) with tirzepatide (which activates GLP-1 receptors) would result in excessive GLP-1 pathway stimulation, likely producing severe gastrointestinal side effects
The middle region of tirzepatide in GLP-1R was stabilized by the peptide-ECD-ECL1-ECL2 interface through both a polar network (T298 45.52b -S11 P -Y205 ECL1 -R299 ECL1 -D15 P -L32 ECD -S31 ECD -Q19 P ) and a complementary nonpolar network with ECD (L32, V36, W39 and Y88), ECL1 (W214), TM1 (L141 1.36b ) and TM2 (L201 2.71b ) via S11 P , Aib13 P , F22 P , W25 P and L26 P (Fig
From a research perspective, these findings are useful because they help define the safety profile of Retatrutide as clinical development progresses