Preliminary clinical evidence suggests that metformin has TSH lowering effects in patients with T2DM and hypothyroidism or in those with TSH serum levels in the upper normal value. Also, metformin may exert a protective role against thyroid nodules growth in patients without insulin-resistance. The cross-talk between tyrosine kinase receptors and the G protein-coupled receptors (which the TSHR belongs to) has been already shown and IRS 1 may represent the hub link between TSHR and IR pathways. By influencing IRS1 phosphorylation pattern, metformin may sensitize TSHR to TSH, thus explaining the findings of clinical studies. However, the existence of this molecular pathway must be confirmed through proper studies and further prospective randomized placebo-controlled studies are needed to confirm this hypothesis.
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