Different effects of metformin on hypothalamic‐pituitary‐thyroid axis activity in levothyroxine‐treated and levothyroxine‐naïve women with non‐autoimmune hypothyroidism

Abstract

What is known and objective 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. Methods The study included two groups of thyroid antibody‐negative women with thyrotrophin levels in the range between 4.5 and 10 mIU/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 6 months with levothyroxine, whereas the second group had not received thyroid hormones. All these women were then managed with metformin (3 g daily). Circulating levels of glucose, insulin, glycated haemoglobin, thyrotrophin, total and free thyroid hormones and prolactin were assessed at baseline and 6 months later. Results and discussion 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 free and 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. What is new and conclusion 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.

Differences in levothyroxine action on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity between metformin‐ and myo‐inositol‐treated women with autoimmune subclinical hypothyroidism

“…Interestingly, the obtained results are in line with the previous findings by Krysiak et al 21 and Casteràs et al 22 The first group of authors observed that levothyroxine/metformin combination therapy was superior to metformin alone in reducing thyrotropin levels in women with non-autoimmune subclinical thyroiditis, whilst the second one that levothyroxine requirements in thyroidectomized diabetic patients on metformin treatment were lower if individuals received metformin.…”

“…Because metformin exerted its maximal effect on hypothalamic–pituitary–thyroid axis activity after 6 months of treatment, 20 the more potent effect of levothyroxine/metformin than levothyroxine/myo‐inositol combination therapy cannot be explained by the fact that the strength of metformin action increased with time. Interestingly, the obtained results are in line with the previous findings by Krysiak et al 21 and Casteràs et al 22 The first group of authors observed that levothyroxine/metformin combination therapy was superior to metformin alone in reducing thyrotropin levels in women with non‐autoimmune subclinical thyroiditis, whilst the second one that levothyroxine requirements in thyroidectomized diabetic patients on metformin treatment were lower if individuals received metformin.…”

Insulin resistance attenuates the impact of levothyroxine on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity in women with autoimmune subclinical hypothyroidism

“…From a theoretical point of view, a stronger impact of levothyroxine in subjects already treated with metformin can be attributed to interactions between metformin and levothyroxine and/or to the effect of metformin. In a recent study, the impact of high‐dose metformin treatment on thyrotropin levels was more pronounced in women simultaneously treated with levothyroxine than in women not receiving this hormone 21 . Although this finding suggests a synergistic action of metformin and levothyroxine, the present study contradicts this explanation.…”