Relationship Between Serum Thyrotropin and Metformin in T2DM
Aim A thyrotropin(TSH)-lowering effect of metformin therapy has been recently reported in patients with type 2 diabetes (T2D) and hypothyroidism. We aimed to evaluate the interplay between metformin therapy and serum TSH concentrations in a group of patients with T2D and normal thyroid function.
Patients and methods Eight hundred and twenty-eight euthyroid patients with T2D (53% women, mean age 65·9 years, median duration of diabetes 10 years) were retrospectively evaluated. There were 250 patients on metformin treatment (30·2%). Serum concentrations of TSH were measured in all subjects.
Results Patients on metformin treatment exhibited significantly higher TSH levels [1·63 (1·11–2·24) mU/l] than those found in patients without metformin [1·40 (1·01–2·24) mU/l, P = 0·009]. We found no significant differences in TSH levels in patients who were on therapy with other oral antidiabetics, antihypertensive drugs or hypolipidemic agents in relation to subjects not taking these drugs. Serum TSH was significantly related to gender, body mass index, hyperlipidaemia and the presence of goitre and diabetic macroangiopathy. In multiple regression analysis with TSH as dependent variable, goitre was negatively related to TSH values. Metformin therapy was a nonsignificant variable in this model.
Conclusion In summary, this is the first survey analysing the relationship between metformin and thyroid function in a large cohort of patients with diabetes. Our data do not support the presence of an independent and significant relationship between TSH values and metformin treatment in euthyroid patients with T2D.
Type 2 diabetes (T2D) and thyroid dysfunction are the most common disorders of the endocrine system occurring in the general population. The association between diabetes and hypothyroidism is known from the sixties. In particular, patients with T2D exhibit a striking high prevalence of thyroid dysfunction, ranging from 5% to 13%, as reported by recent retrospective and prospective studies. Metformin, an oral hypoglycaemic biguanide, has been used for the treatment for T2D for many years, and recently, it is considered the first choice for oral treatment for T2D patients in the absence of contraindications.
Metformin is considered a safe drug with few pharmacological interactions. Several retrospective and prospective studies in a limited number of patients have suggested that therapy with this agent is associated with a significant reduction in serum thyrotropin (TSH) concentrations, without relevant changes in serum thyroxine (T4) and triiodothyronine (T3) levels. This finding has been reported in diabetic patients with primary hypothyroidism both under replacement therapy and untreated. The prospective study by Cappelli et al., however, did not report any significant effect of metformin treatment in a group of 54 patients with T2D and intact pituitary–thyroid axis. Furthermore, in a recent study, we have reported that newly diagnosed hypothyroidism in patients with T2D was significantly and directly related not only with thyroid autoimmunity, but also with metformin therapy. These findings suggest an independent association of metformin treatment with newly diagnosed hypothyroidism in patients with diabetes.
To our knowledge, there are no surveys analysing the relationship between metformin and thyroid function in large cohorts of diabetic patients with normal thyroid function. Therefore, the aim of the present study has been to evaluate serum TSH levels in euthyroid patients with T2D, and their relationship with metformin and other antidiabetic treatments in a cross-sectional design.
Abstract and Introduction
Abstract
Aim A thyrotropin(TSH)-lowering effect of metformin therapy has been recently reported in patients with type 2 diabetes (T2D) and hypothyroidism. We aimed to evaluate the interplay between metformin therapy and serum TSH concentrations in a group of patients with T2D and normal thyroid function.
Patients and methods Eight hundred and twenty-eight euthyroid patients with T2D (53% women, mean age 65·9 years, median duration of diabetes 10 years) were retrospectively evaluated. There were 250 patients on metformin treatment (30·2%). Serum concentrations of TSH were measured in all subjects.
Results Patients on metformin treatment exhibited significantly higher TSH levels [1·63 (1·11–2·24) mU/l] than those found in patients without metformin [1·40 (1·01–2·24) mU/l, P = 0·009]. We found no significant differences in TSH levels in patients who were on therapy with other oral antidiabetics, antihypertensive drugs or hypolipidemic agents in relation to subjects not taking these drugs. Serum TSH was significantly related to gender, body mass index, hyperlipidaemia and the presence of goitre and diabetic macroangiopathy. In multiple regression analysis with TSH as dependent variable, goitre was negatively related to TSH values. Metformin therapy was a nonsignificant variable in this model.
Conclusion In summary, this is the first survey analysing the relationship between metformin and thyroid function in a large cohort of patients with diabetes. Our data do not support the presence of an independent and significant relationship between TSH values and metformin treatment in euthyroid patients with T2D.
Introduction
Type 2 diabetes (T2D) and thyroid dysfunction are the most common disorders of the endocrine system occurring in the general population. The association between diabetes and hypothyroidism is known from the sixties. In particular, patients with T2D exhibit a striking high prevalence of thyroid dysfunction, ranging from 5% to 13%, as reported by recent retrospective and prospective studies. Metformin, an oral hypoglycaemic biguanide, has been used for the treatment for T2D for many years, and recently, it is considered the first choice for oral treatment for T2D patients in the absence of contraindications.
Metformin is considered a safe drug with few pharmacological interactions. Several retrospective and prospective studies in a limited number of patients have suggested that therapy with this agent is associated with a significant reduction in serum thyrotropin (TSH) concentrations, without relevant changes in serum thyroxine (T4) and triiodothyronine (T3) levels. This finding has been reported in diabetic patients with primary hypothyroidism both under replacement therapy and untreated. The prospective study by Cappelli et al., however, did not report any significant effect of metformin treatment in a group of 54 patients with T2D and intact pituitary–thyroid axis. Furthermore, in a recent study, we have reported that newly diagnosed hypothyroidism in patients with T2D was significantly and directly related not only with thyroid autoimmunity, but also with metformin therapy. These findings suggest an independent association of metformin treatment with newly diagnosed hypothyroidism in patients with diabetes.
To our knowledge, there are no surveys analysing the relationship between metformin and thyroid function in large cohorts of diabetic patients with normal thyroid function. Therefore, the aim of the present study has been to evaluate serum TSH levels in euthyroid patients with T2D, and their relationship with metformin and other antidiabetic treatments in a cross-sectional design.
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