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TM2, in particular, adopts a conformation in the orforglipron-bound structure that would be difficult to predict computationally, highlighting the receptor's conformational flexibility and the inherent limitations of structure-based drug design for class B GPCRs

Its a big shift, and it has also created a lot of confusion

The documented research protocol starts at 2 mg once weekly and escalates stepwise roughly every four weeks toward maintenance targets such as 4, 8, and 12 mg

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