Effects of Treatment With Metformin on TSH Levels: A Meta-analysis of Literature Studies

Abstract

Some data suggest that metformin affects the thyroid profile in patients with type 2 diabetes, but contrasting results are reported in different settings. The aim of this meta-analysis was to assess the effect of metformin treatment on TSH in subjects with or without thyroid dysfunction. We performed a systematic search of articles evaluating changes in TSH levels in patients receiving metformin. Studies evaluating TSH levels before and after metformin treatment were included. Clinical data, demographic variables, and TSH levels before and after treatment with metformin were extracted. Data were analyzed according to the underlying thyroid disease. A total of 7 datasets (206 patients) were included in the final analysis. After metformin treatment, a slight but significant reduction in TSH levels was found in 4 datasets on 119 patients with overt hypothyroidism receiving l-T4 replacement (mean difference, 1.08; 95% confidence interval [CI], 0.50, 1.65; P=.0003). Similarly, in 2 datasets reporting on a total of 33 patients with subclinical hypothyroidism not receiving treatment with l-T4, a significant reduction in TSH levels was reported (mean difference, 1.59; 95% CI, 1.32, 1.87; P<.00001) after treatment with metformin. In 1 dataset, including 54 euthyroid patients not receiving l-T4, no changes in TSH levels were reported after treatment with metformin (mean difference, 0.18; 95% CI, -0.20, 0.56; P=.35). Metformin induces a reduction in TSH levels both in overt and in subclinical hypothyroidism. In contrast, no change in TSH levels is found in euthyroid patients.