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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

But the human data gap is real

There is no evidence that doses above 500mcg produce proportionally better results, and clinical trials using 1mg daily did not dramatically outperform lower doses

Seek urgent GP assessment if you experience progressive neurological symptoms, as delayed treatment may result in irreversible nerve damage

Surendran S, Adaikalakoteswari A, Saravanan P, Shatwaan IA, Lovegrove JA, Vimaleswaran KS

93.Hancock AA, Bennani YL, Bush EN, et al