Abstract

Metformin was found to reduce thyrotrophin levels in subjects with hypothyroidism. This case-control study was aimed at comparing metformin action on hypothalamic-pituitary-thyroid axis activity between levothyroxine-treated and levothyroxine-naïve women with non-autoimmune thyroid hypofunction. The study included two groups of thyroid antibody-negative women with thyrotrophin levels in the range between 4.5 and 10mIU/L and untreated prediabetes, matched for age, body mass index, thyrotrophin levels and glucose homeostasis markers. The first group had been treated for at least 6months with levothyroxine, whereas the second group had not received thyroid hormones. All these women were then managed with metformin (3g daily). Circulating levels of glucose, insulin, glycated haemoglobin, thyrotrophin, total and free thyroid hormones and prolactin were assessed at baseline and 6months later. Thirty-two women (16 in each treatment arm) completed the study. At baseline, both groups differed only in free and total thyroxine levels. Metformin reduced glucose levels and glycated haemoglobin, improved insulin sensitivity and decreased thyrotrophin levels. The impact on insulin sensitivity and thyrotrophin was stronger in women simultaneously treated with levothyroxine than in women not receiving this hormone. In levothyroxine-treated patients, metformin slightly reduced prolactin levels. In both study groups, metformin treatment exerted a neutral effect on freeand total thyroxine and triiodothyronine. The thyrotrophin-lowering effect of metformin correlated with the improvement in insulin sensitivity and in levothyroxine-treated women with the changes in prolactin levels. The obtained results suggest that metformin/levothyroxine combination therapy may be an interesting treatment option in women with non-autoimmune hypothyroidism poorly tolerating high-dose levothyroxine treatment.

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