Endocrine

, Volume 59, Issue 1, pp 66–71 | Cite as

Metformin effect on TSH in subclinical hypothyroidism: randomized, double-blind, placebo-controlled clinical trial

  • Mateus Dornelles Severo
  • Thais Stürmer Andrade
  • Vicente Correa Junior
  • Alexandre Antonio Naujorks
  • Miguel Gus
  • Beatriz D. Schaan
Endocrine Trials
  • 152 Downloads

Abstract

Introduction

Non-randomized trials suggest that metformin may reduce TSH levels through unknown mechanisms.

Objective

To evaluate whether metformin can reduce TSH levels in subjects with subclinical hypothyroidism.

Patients and methods

This is a randomized, double-blind, placebo controlled clinical trial with 3 months duration that enrolled 48 individuals, between 18 and 65 years, with subclinical hypothyroidism. The patients were randomized to the use of metformin 850 mg or placebo twice a day for 3 months. The primary outcome was the absolute decrease in TSH levels. Secondary outcomes were changes in the clinical and laboratory assessment, as well as in blood pressure assessed by ambulatory blood pressure monitoring.

Results

After 3 months, 93.75% of participants completed the follow-up. The post treatment value of TSH in the metformin and placebo groups were 6.48 ± 3.11 and 7.02 ± 3.28 mIU/L, respectively (p = 0.57). Patients who achieved status of euthyroidism in the metformin and placebo groups were 21.7 and 18.2%, respectively (p = 0.76). There was no significant reduction of TSH within the groups [delta for TSH of 0.63 ± 0.56 (p = 0.28) and 0.54 ± 0.60 mIU/L (p = 0.38), in metformin and placebo groups, respectively]. There was a small increase in HDL cholesterol (1.62 ± 0.45 vs. 1.34 ± 0.39 mmol/L, p = 0.03) favoring the metformin group.

Conclusion

Since the sample size was small, the study was inconclusive and the results should be considered preliminary data of a study that needs to enroll 1626 patients to show a 0.5 mIU/L difference in TSH between the groups, with 90% power.

Keywords

TSH Metformin Subclinical hypothyroidism Clinical trial 

Notes

Acknowledgements

Fundo de Incentivo a Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE-HCPA) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

References

  1. 1.
    B. Biondi, D.S. Cooper, The clinical significance of subclinical thyroid dysfunction. Endocr. Rev. 29(1), 76–131 (2008)CrossRefPubMedGoogle Scholar
  2. 2.
    J.G. Hollowell, N.W. Staehling, W.D. Flanders et al., Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 87(2), 489–499 (2002)CrossRefPubMedGoogle Scholar
  3. 3.
    J.A. Sgarbi, P.F. Teixeira, L.M. Maciel et al., The Brazilian consensus for the clinical approach and treatment of subclinical hypothyroidism in adults: recommendations of the thyroid Department of the Brazilian Society of Endocrinology and Metabolism. Arq. Bras. Endocrinol. Metabol. 57(3), 166–183 (2013)CrossRefPubMedGoogle Scholar
  4. 4.
    N. Rodondi, W.P. den Elzen, D.C. Bauer et al., Subclinical hypothyroidism and the risk of coronary heart disease and mortality. J. Am. Med. Assoc. 304(12), 1365–1374 (2010)CrossRefGoogle Scholar
  5. 5.
    V. Kotsis, M. Alevizaki, S. Stabouli et al., Hypertension and hypothyroidism: results from an ambulatory blood pressure monitoring study. J. Hypertens. 25(5), 993–999 (2007)CrossRefPubMedGoogle Scholar
  6. 6.
    H.C. Villar, H. Saconato, O. Valente et al., Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst. Rev. 18(3), CD003419 (2007).Google Scholar
  7. 7.
    R. Lupoli, A. Di Minno, A. Tortora et al., Effects of treatment with metformin on TSH levels: a meta-analysis of literature studies. J. Clin. Endocrinol. Metab. 99(1), E143–E148 (2014)CrossRefPubMedGoogle Scholar
  8. 8.
    M.L. Isidro, M.A. Penín, R. Nemiña et al., Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy. Endocrine 32(1), 79–82 (2007)CrossRefPubMedGoogle Scholar
  9. 9.
    C. Cappelli, M. Rotondi, I. Pirola et al., TSH-lowering effect of metformin in type 2 diabetic patients: differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients. Diabetes Care 32(9), 1589–1590 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    R.A. Vigersky, A. Filmore-Nassar, A.R. Glass, Thyrotropin suppression by metformin. J. Clin. Endocrinol. Metab. 91(1), 225–227 (2006)CrossRefPubMedGoogle Scholar
  11. 11.
    S. Morteza Taghavi, H. Rokni, S. Fatemi, Metformin decreases thyrotropin in overweight women with polycystic ovarian syndrome and hypothyroidism. Diabetes Vasc. Dis. Res. 8(1), 47–48 (2011)CrossRefGoogle Scholar
  12. 12.
    J. Meyerovitch, P. Rotman-Pikielny, M. Sherf et al., Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians. Arch. Intern. Med. 167(14), 1533–1538 (2007)CrossRefPubMedGoogle Scholar
  13. 13.
    M. Karimifar, A. Aminorroaya, M. Amini et al., Effect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes: a randomized placebo-controlled clinical trial. J. Res. Med. Sci. 19(11), 1019–1026 (2014)PubMedPubMedCentralGoogle Scholar
  14. 14.
    R. Krysiak, W. Szkróbka, B. Okopień, Sex-dependent effect of metformin on hypothalamic-pituitary-thyroid axis activity in patients with subclinical hypothyroidism. Pharmacol. Rep. 68(6), 1115–1119 (2016)CrossRefPubMedGoogle Scholar
  15. 15.
    E. Selvin, S. Bolen, H.C. Yeh et al., Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch. Intern. Med. 168(19), 2070–2080 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    K. Landin-Wilhelmsen, Metformin and blood pressure. J. Clin. Pharm. Ther. 17(2), 75–79 (1992)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Mateus Dornelles Severo
    • 1
  • Thais Stürmer Andrade
    • 1
  • Vicente Correa Junior
    • 2
  • Alexandre Antonio Naujorks
    • 3
  • Miguel Gus
    • 2
  • Beatriz D. Schaan
    • 1
    • 4
  1. 1.Programa de Pós-Graduação em EndocrinologiaUniversidade Federal do Rio Grande do Sul, Faculdade de MedicinaPorto AlegreBrazil
  2. 2.Programa de Pós-Graduação em CardiologiaUniversidade Federal do Rio Grande do Sul, Faculdade de MedicinaPorto AlegreBrazil
  3. 3.Universidade Federal de Santa MariaSanta MariaBrazil
  4. 4.Hospital de Clínicas de Porto AlegrePorto AlegreBrazil

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