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A casecontrol study showed a higher risk of developing breast cancer in women with two specific single nucleotide polymorphisms in the POLK gene compared with controls 48

However, the full effects might take several months to manifest, with the most significant changes typically noted throughout 26 to 52 weeks

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This concept eventually led to drugs like sitagliptin (approved 2006), but those would generally have less potent effects than direct GLP-1 agonists since GLP-1 levels only double or triple on DPP-4 inhibitors (and those drugs rely on some residual pancreatic function and meal stimulation) ( [59] )