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Similar G protein interface was also observed in the tirzepatide-bound GLP-1R except for the orientation of E262 ICL2 that is closer to that of GLP-1

Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASSCVOT design and baseline characteristics

Arnett DK, Blumenthal RS, Albert MA, et al

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Such relative instability of the peptide in vivo , compared to the antibody component, will lead to suboptimal efficacy of the fusion molecule