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Most berberine research involves oral supplementation where the compound interacts with the gut - transdermal delivery bypasses the gut entirely

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doi: 10.1016/j.tibs.2009.02.004

During the tests, rats and shrews administered with GEP44 showed no signs of nausea or vomiting, possibly due to the activation of multiple receptors canceling out the intracellular signaling pathway responsible for those symptoms

These medications carry a boxed warning regarding thyroid C-cell tumor risk observed in rodent studies and are contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2)

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