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Rohmann N, Schlicht K, Geisler C, Hollstein T, Knappe C, Krause L, et al

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(2015) found that the hypoglycemic effect of metformin was reduced by blocking the cAMP pathway in the gut, and speculated that the target of metformin was mainly in the gut

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In addition, with sustained stimulation, there will be fewer receptors available on the cell surface due to receptor desensitization and internalization