The ratio of free triiodothyronine to free thyroxine is regulated differently in patients with type 2 diabetes mellitus treated and not treated with sodium glucose cotransporter 2 inhibitors

Background and aims: Triiodothyronine reduces sodium glucose cotransporter 2 expression in the kidney and increased glucose excretion in urine of alloxan-induced diabetic rats. Free thyroxine is also negatively associated with islet beta-cell function in euthyroid subjects. However, the influence of sodium glucose cotransporter 2 inhibitor on thyroid function in patients with type 2 diabetes mellitus has not been established.

Methods: We investigated thyroid function in patients with type 2 diabetes mellitus in the presence or absence of sodium glucose cotransporter 2 inhibitor in a multicenter retrospective study conducted between 2019 and 2021. All participants visited the hospital monthly for type 2 diabetes mellitus treatment and plasma glucose and glycated hemoglobin level measurements. Furthermore, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine levels were measured annually.

Results: Free triiodothyronine level and the free triiodothyronine:free thyroxine ratio in the group treated with sodium glucose cotransporter 2 inhibitor were significantly higher than the levels in the group not treated with sodium glucose cotransporter 2 inhibitor. Free triiodothyronine levels in the group treated with sodium glucose cotransporter 2 inhibitor were significantly higher than the levels in the group not treated with sodium glucose cotransporter 2 inhibitor (p = 0.040). Free thyroxine levels in the group treated with sodium glucose cotransporter 2 inhibitor were significantly lower than the levels in the group not treated with sodium glucose cotransporter 2 inhibitor (p = 0.002). Thyroid-stimulating hormone levels did not differ significantly between the two groups.

Conclusions: Our findings show that sodium glucose cotransporter 2 inhibitor affects free triiodothyronine levels free thyroxine levels, and the free triiodothyronine:free thyroxine ratio.