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In rodent studies, tirzepatide and other GLP-1 receptor agonists caused dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures

[115] This functionality is lost in vitamin B 12 deficiency, resulting in an increased homocysteine level and the trapping of folate as 5-methyl-tetrahydrofolate, from which THF (the active form of folate) cannot be recovered

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At the molecular level, preclinical models have suggested a multimodal mechanism