Metformin reduces risk of benign nodular goiter in patients with type 2 diabetes mellitus

in European Journal of Endocrinology
Correspondence should be addressed to C-H Tseng; Email: ccktsh@ms6.hinet.net
Restricted access

Background

Whether metformin might affect the risk of benign nodular goiter in patients with type 2 diabetes mellitus has not been investigated.

Methods

Patients with new-onset type 2 diabetes mellitus during 1999–2005 were enrolled from Taiwan’s National Health Insurance database. Analyses were conducted in a propensity score matched-pairs of 20,048 ever users and 20,048 never users of metformin. The patients were followed until December 31, 2011, for the incidence of benign nodular goiter. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the propensity score.

Results

Among the never users and ever users of metformin, 392 and 221 cases were diagnosed of benign nodular goiter during follow-up, with incidence of 457.88 and 242.45 per 100,000 person-years, respectively. The overall hazard ratio for ever versus never users was 0.527 (95% confidence interval: 0.447–0.621). When cumulative duration of metformin therapy was divided into tertiles, the hazard ratios for the first (<25.3 months), second (25.3–57.3 months) and third (>57.3 months) tertiles were 0.815 (0.643–1.034), 0.648 (0.517–0.812) and 0.255 (0.187–0.348), respectively. Sensitivity analyses estimating the overall hazard ratios for patients enrolled in each specific year from 1999 to 2005 consistently showed a lower risk of benign nodular goiter among users of metformin.

Conclusion

Metformin use is associated with a lower risk of benign nodular goiter in patients with type 2 diabetes mellitus.

 

     European Society of Endocrinology

Related Articles

Article Information

Metrics

All Time Past Year Past 30 Days
Abstract Views 652 652 64
Full Text Views 105 105 5
PDF Downloads 43 43 5

Altmetrics

Figures

  • View in gallery

    Flowchart showing the procedures in creating a cohort of 1:1 matched-pairs of metformin ever and never users from the reimbursement database of the National Health Insurance.

References

  • 1

    TsatsoulisA. The role of insulin resistance/hyperinsulinism on the rising trend of thyroid and adrenal nodular disease in the current environment. Journal of Clinical Medicine 2018 7 E37. (https://doi.org/10.3390/jcm7030037)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    MalaguarneraRVellaVNicolosiMLBelfioreA. Insulin resistance: any role in the changing epidemiology of thyroid cancer? Frontiers in Endocrinology 2017 8 314. (https://doi.org/10.3389/fendo.2017.00314)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    HeidariZAbdaniMMansourniaMA. Insulin resistance associated with differentiated thyroid carcinoma: penalized conditional logistic regression analysis of a matched case-control study data. International Journal of Endocrinology and Metabolism 2018 16 e14545. (https://doi.org/10.5812/ijem.14545)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    WangYWHeSJFengXChengJLuoYTTianLHuangQ. Metformin: a review of its potential indications. Drug Design Development and Therapy 2017 11 24212429. (https://doi.org/10.2147/DDDT.S141675)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    TsengCH. Metformin reduces thyroid cancer risk in Taiwanese patients with type 2 diabetes. PLoS ONE 2014 9 e109852. (https://doi.org/10.1371/journal.pone.0109852)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    ChoYYKangMJKimSKJungJHHahmJRKimTHNamJYLeeBWLeeYHChungJH Protective effect of metformin against thyroid cancer development: a population-based study in Korea. Thyroid 2018 28 864870. (https://doi.org/10.1089/thy.2017.0550)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    TsengCH. Thyroid cancer risk is not increased in diabetic patients. PLoS ONE 2012 7 e53096. (https://doi.org/10.1371/journal.pone.0053096)

  • 8

    BaileyCJ. Metformin: historical overview. Diabetologia 2017 60 15661576. (https://doi.org/10.1007/s00125-017-4318-z)

  • 9

    GlynnNHannonMJLewisSHilleryPAl-MousaMHillADKeelingFMorrinMThompsonCJSmithD Utility of repeat cytological assessment of thyroid nodules initially classified as benign: clinical insights from multidisciplinary care in an Irish tertiary referral centre. BMC Endocrine Disorders 2016 16 45. (https://doi.org/10.1186/s12902-016-0125-7)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    TsengCH. Metformin is associated with a lower risk of colorectal cancer in Taiwanese patients with type 2 diabetes: a retrospective cohort analysis. Diabetes and Metabolism 2017 43 438445. (https://doi.org/10.1016/j.diabet.2017.03.004)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    TsengCH. Metformin and lung cancer risk in patients with type 2 diabetes mellitus. Oncotarget 2017 8 4113241142. (https://doi.org/10.18632/oncotarget.17066)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    ParsonsLS. Performing a 1:N case-control match on propensity score. (available at: http://www.google.com.tw/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CBsQFjAAahUKEwibi7HllcnIAhUDoJQKHVeZA9A&url=http%3A%2F%2Fwww2.sas.com%2Fproceedings%2Fsugi29%2F165-29.pdf&usg=AFQjCNFOHGWYu8E8Bn4-Bo1TUiJKtT987Q). Accessed on 19 March 2019.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    AustinPCStuartEA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Statistics in Medicine 2015 34 36613679. (https://doi.org/10.1002/sim.6607)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    AustinPC. The performance of different propensity score methods for estimating marginal hazard ratios. Statistics in Medicine 2013 32 28372849. (https://doi.org/10.1002/sim.5705)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    MengXXuSChenGDerwahlMLiuC. Metformin and thyroid disease. Journal of Endocrinology 2017 233 R43R51. (https://doi.org/10.1530/JOE-16-0450)

  • 16

    RenaGPearsonERSakamotoK. Molecular mechanism of action of metformin: old or new insights? Diabetologia 2013 56 18981906. (https://doi.org/10.1007/s00125-013-2991-0)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    ViolletBGuigasBSanz GarciaNLeclercJForetzMAndreelliF. Cellular and molecular mechanisms of metformin: an overview. Clinical Science 2012 122 253270. (https://doi.org/10.1042/CS20110386)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    HurKYLeeMS. New mechanisms of metformin action: focusing on mitochondria and the gut. Journal of Diabetes Investigation 2015 6 600609. (https://doi.org/10.1111/jdi.12328)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    MorshedSAMaRLatifRDaviesTF. How one TSH receptor antibody induces thyrocyte proliferation while another induces apoptosis. Journal of Autoimmunity 2013 47 1724. (https://doi.org/10.1016/j.jaut.2013.07.009)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    MallikRChowdhuryTA. Metformin in cancer. Diabetes Research and Clinical Practice 2018 143 409419. (https://doi.org/10.1016/j.diabres.2018.05.023)

  • 21

    HuXLiuYWangCHouLZhengXXuYDingLPangS. Metformin affects thyroid function in male rats. Oncotarget 2017 8 107589107595. (https://doi.org/10.18632/oncotarget.22536)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    RăcătăianuNBolboacăSDSitar-TăutAVMârzaSMogaDValeaAGhervanC. The effect of metformin treatment in obese insulin-resistant patients with euthyroid goiter. Acta Clinica Belgica 2018 73 317323. (https://doi.org/10.1080/17843286.2018.1439273)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    SuiMYuYZhangHDiHLiuCFanY. Efficacy of metformin for benign thyroid nodules in subjects with insulin resistance: a systematic review and meta-analysis. Frontiers in Endocrinology 2018 9 494. (https://doi.org/10.3389/fendo.2018.00494)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    HeXWuDHuCXuTLiuYLiuCXuBTangW. Role of metformin in the treatment of patients with thyroid nodules and insulin resistance: a systematic review and meta-analysis. Thyroid 2019 29 359367. (https://doi.org/10.1089/thy.2017.0707)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    LévesqueLEHanleyJAKezouhASuissaS. Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ 2010 340 b5087. (https://doi.org/10.1136/bmj.b5087)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    KnudsenNBrixTH. Genetic and non-iodine-related factors in the aetiology of nodular goitre. Best Practice and Research: Clinical Endocrinology and Metabolism 2014 28 495506. (https://doi.org/10.1016/j.beem.2014.02.005)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    CohenRNDavisAM. Management of adult patients with thyroid nodules and differentiated thyroid cancer. JAMA 2017 317 434435. (https://doi.org/10.1001/jama.2016.18420)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

PubMed

Google Scholar