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154 However, HIF-1 in islets is decreased in T2D, by hyperglycemia through inhibiting the HIF-1-HIF-1 dimer formation, and by NEFAs through increasing the proteolysis, leading to inability to initiate hypoxic adaptive responses

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If the cell cannot recycle GSSG back into GSH fast enough using an enzyme called glutathione reductase, the cell enters a state of toxic oxidative stress, leading to mitochondrial damage and, eventually, programmed cell death (apoptosis)

The rate of dropout in studies of oral semaglutide has been significant, approximately 25% in recent trials, reflecting tolerability concerns, mainly due to nausea (source)

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