Metformin Does Not Suppress Serum Thyrotropin by Increasing Levothyroxine Absorption

Abstract

Background: Levothyroxine (LT4) absorption is affected by concomitant ingestion of certain minerals, medications, and foods. It has been hypothesized that metformin may suppress serum thyrotropin (TSH) concentrations by enhancing LT4 absorption or by directly affecting the hypothalamic-pituitary axis. This study examined the effect of metformin ingestion on LT4 absorption, as assessed by serum total thyroxine (TT4) concentrations. Methods: A modified Food and Drug Administration LT4 bioequivalence protocol was applied to healthy, metformin-naïve, euthyroid adult volunteers. Following an overnight fast, 600 lg LT4 was administered orally. Serum TT4 concentrations were measured at baseline and at 0.5, 1, 1.5, 2, 4, and 6 h following LT4 administration. Measurements were performed before and after one week of metformin ingestion (850 mg three times daily). Peak serum TT4 concentrations, time to peak TT4 concentrations, and area under the concentration-time curve (AUC) were calculated. Results: Twenty-six subjects (54% men, 27% white, age 33 -10 years) were studied. There were no significant differences in peak serum TT4 concentrations ( p = 0.13) and time to peak TT4 concentrations ( p = 0.19) before and after one week of metformin use. A trend toward reduced TT4 AUC was observed after metformin ingestion (pre-metformin 3893 -568 lg/dL-min, post-metformin 3765 -588 lg/dL-min, p = 0.09). Conclusions: LT4 absorption is unchanged by concomitant metformin ingestion. Mechanisms other than increased LT4 absorption may be responsible for the suppressed TSH concentrations observed in patients ingesting both drugs.

Association between Thyroid Function and Nonalcoholic Fatty Liver Disease in Euthyroid Type 2 Diabetes Patients

“…In a prospective study, increased metformin use was associated with low TSH levels among patients with treated hypothyroidism but not those with normal thyroid function [ 22 ]. A study by Al-Alusi et al shows that metformin suppressed serum TSH levels independent of increasing levothyroxine absorption [ 23 ]. Cappelli et al found a significant decrease in TSH levels in euthyroid patients with higher baseline TSH concentrations after metformin therapy [ 9 ].…”

Metformin and thyroid disease

“…In most studies, there was no increase of serum thyroid hormone level in response to metformin, irrespective of thyroxin replacement or not. A clinical study concluded that levothyroxine (l-T 4 ) absorption is unchanged by concomitant metformin intake (Al-Alusi et al 2015). In addition, metformin is not known to increase the absorption of any other nutrients or drugs.…”

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

“…They cannot be also related to the effect on levothyroxine absorption, which has not been affected by concomitant metformin ingestion. 27 Finally, similar baseline and posttreatment values of the body mass index and waist circumference are an argument against their association with a weight-reducing effect of metformin, as suggested by Casteràs et al 22 In case of metformin, this association may be explained by metformin action on adenosine 5 0monophosphate-activated protein kinase, which both regulates energy homeostasis and glucose balance, 28 and directly affects thyrotropin and other pituitary hormone secretion. 29 In turn, myo-inositol modulates the glycosyl phosphatidylinositol/inositol phosphate glycan signalling pathway, acting as a messenger of thyrotropin and insulin action.…”

“…However, at the beginning of the current study, glucose homeostasis markers did not differ between the study groups and therefore differences in insulin‐sensitizing potencies of metformin and myo‐inositol cannot explain our findings. They cannot be also related to the effect on levothyroxine absorption, which has not been affected by concomitant metformin ingestion 27 . Finally, similar baseline and post‐treatment values of the body mass index and waist circumference are an argument against their association with a weight‐reducing effect of metformin, as suggested by Casteràs et al 22 In case of metformin, this association may be explained by metformin action on adenosine 5′‐monophosphate‐activated protein kinase, which both regulates energy homeostasis and glucose balance, 28 and directly affects thyrotropin and other pituitary hormone secretion 29 .…”