Effects of treatment with metformin on TSH levels: a meta-analysis of literature studies

J Clin Endocrinol Metab. 2014 Jan;99(1):E143-8. doi: 10.1210/jc.2013-2965. Epub 2013 Dec 20.


Context: Some data suggest that metformin affects the thyroid profile in patients with type 2 diabetes, but contrasting results are reported in different settings.

Objective: The aim of this meta-analysis was to assess the effect of metformin treatment on TSH in subjects with or without thyroid dysfunction.

Data sources: We performed a systematic search of articles evaluating changes in TSH levels in patients receiving metformin.

Study selection: Studies evaluating TSH levels before and after metformin treatment were included.

Data extraction: Clinical data, demographic variables, and TSH levels before and after treatment with metformin were extracted. Data were analyzed according to the underlying thyroid disease.

Data synthesis: 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).

Conclusions: 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.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Hormone Replacement Therapy
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Hypothyroidism / blood
  • Hypothyroidism / chemically induced
  • Hypothyroidism / drug therapy
  • Hypothyroidism / epidemiology
  • Metformin / therapeutic use*
  • Thyrotropin / blood*
  • Thyrotropin / drug effects*
  • Thyroxine / therapeutic use


  • Hypoglycemic Agents
  • Thyrotropin
  • Metformin
  • Thyroxine