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Safety Considerations and Contraindications Absolute contraindications include personal or family history of medullary thyroid carcinoma, severe pancreatic disease, or uncontrolled diabetic retinopathy in some cases

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A previous clinical trial aimed at correcting the HHcy induced by metformin in PCOS patients found that metformin did indeed significantly increase circulating Hcy and that folic acid reduced it only by 8% compared to a 21% reduction with a multivitaminic approach (B1, B6, and B12) [24]

therefore, on the basis of the decision of the local Ethics Committee of Toho University Omori Medical Center, informed consent was not required

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