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J Clin Invest (1991) 88:178592.10.1172/JCI115499 33 De NigrisFLermanLOCondorelliMLermanANapoliC

Although a majority of oral drugs are absorbed in the small intestine, studies indicate that oral semaglutide is likely absorbed in the stomach

There are several reasons behind this recommendation

The freeze-thaw cycle can damage the delicate peptide structure, a process called denaturation, which can reduce its effectiveness

Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons

Therefore, the reduction in its effect observed by year five likely reflects the cessation of therapy rather than the development of pharmacologic tolerance or adaptation