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Whereas these compounds showed toxicity at high concentrations with an unusual bell-shaped doseresponse curve, they induced glucose-dependent insulin release from normal mouse islets but not from GLP-1R knockout mice

However, a crucial limitation of the above studies is that the endpoint was pathologic (described as asymptomatic chronic pancreatitis), referring to histologic changes, rather than clinical 26

Cephalalgia, 37:581-591

Abstract #0849, ACR Convergence 2025, Chicago, IL (October 2429, 2025)

In comparative studies, complete suppression of -arrestin recruitment produced slower internalization, reduced downregulation, and longer-lasting cAMP signaling than semaglutide [52], indicating that semaglutide retains functionally meaningful arrestin engagement, even if not at the highest level among GLP-1R agonists

I tell patients not to panicit happens more often than people admit