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The oral route of drug delivery is challenging for peptides because the GI tract is specifically designed to break down proteins and peptides into their constituent amino acids for absorption

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A retrospective study looking at concomitant use of proton pump inhibitors (PPIs) alongside metformin in 614 people with type 2 diabetes in the US found a significant reduction in B12 levels of 34% in patients taking both medications, compared to controls taking either drug alone (Long et al, 2012)