Protective Effect of Metformin Against Thyroid Cancer Development: A Population-Based Study in Korea

Yoon Young Cho, Min Jin Kang, Soo Kyoung Kim, Jung Hwa Jung, Jong Ryeal Hahm, Tae Hyuk Kim, Joo Young Nam, byungwan lee, Yong Ho Lee, Jae Hoon Chung, Sun Ok Song, Sun Wook Kim

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Abstract

Background: Metformin, the most widely used drug for type 2 diabetes, has recently attracted attention with regard to its antitumor activity. However, clinical studies have yielded conflicting results regarding the association between metformin and thyroid cancer development, despite its antitumor effect in preclinical studies. Methods: This is a retrospective cohort study using the Korean National Health Insurance claim database. Matched populations of 128,453 metformin users and 128,453 non-users were analyzed for thyroid cancer incidence. Metformin users were categorized into lowest, middle, and highest tertiles according to cumulative dose or duration of metformin therapy. Results: Thyroid cancer developed in 340 (0.26%) metformin users and 487 (0.38%) non-users during a mean follow-up of 7.2 years (hazard ratio = 0.69 [confidence interval 0.60-0.79]; p < 0.001). The incidence of thyroid cancer per 10 5 person-years was 51.6 in metformin non-users. For metformin users, the incidence was 84.5 for <529,000 mg, 20.6 for 529,000-1,007,799 mg, and 6.3 for >1,007,799 mg; 86.3 for <1085 days, 20.3 for 1085-2094 days, and 4.7 for >2094 days for duration of therapy. The hazard ratio for thyroid cancer decreased significantly in metformin users as a function of dose and duration of metformin therapy. Conclusions: Metformin appears to be associated with a preventive effect on thyroid cancer development in a nationwide population-based study, but is not effective in the early phase of treatment. Considering the increasing prevalence of obesity and the role of insulin resistance in the development of cancer, metformin might be the preferred treatment for its dual anti-diabetic and antitumor effects.

Original languageEnglish
Pages (from-to)864-870
Number of pages7
JournalThyroid
Volume28
Issue number7
DOIs
Publication statusPublished - 2018 Jul 1

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Metformin
Korea
Thyroid Neoplasms
Population
National Health Programs
Type 2 Diabetes Mellitus
Insulin Resistance
Cohort Studies
Therapeutics
Retrospective Studies
Obesity
Databases
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Cho, Y. Y., Kang, M. J., Kim, S. K., Jung, J. H., Hahm, J. R., Kim, T. H., ... Kim, S. W. (2018). Protective Effect of Metformin Against Thyroid Cancer Development: A Population-Based Study in Korea. Thyroid, 28(7), 864-870. https://doi.org/10.1089/thy.2017.0550
Cho, Yoon Young ; Kang, Min Jin ; Kim, Soo Kyoung ; Jung, Jung Hwa ; Hahm, Jong Ryeal ; Kim, Tae Hyuk ; Nam, Joo Young ; lee, byungwan ; Lee, Yong Ho ; Chung, Jae Hoon ; Song, Sun Ok ; Kim, Sun Wook. / Protective Effect of Metformin Against Thyroid Cancer Development : A Population-Based Study in Korea. In: Thyroid. 2018 ; Vol. 28, No. 7. pp. 864-870.
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title = "Protective Effect of Metformin Against Thyroid Cancer Development: A Population-Based Study in Korea",
abstract = "Background: Metformin, the most widely used drug for type 2 diabetes, has recently attracted attention with regard to its antitumor activity. However, clinical studies have yielded conflicting results regarding the association between metformin and thyroid cancer development, despite its antitumor effect in preclinical studies. Methods: This is a retrospective cohort study using the Korean National Health Insurance claim database. Matched populations of 128,453 metformin users and 128,453 non-users were analyzed for thyroid cancer incidence. Metformin users were categorized into lowest, middle, and highest tertiles according to cumulative dose or duration of metformin therapy. Results: Thyroid cancer developed in 340 (0.26{\%}) metformin users and 487 (0.38{\%}) non-users during a mean follow-up of 7.2 years (hazard ratio = 0.69 [confidence interval 0.60-0.79]; p < 0.001). The incidence of thyroid cancer per 10 5 person-years was 51.6 in metformin non-users. For metformin users, the incidence was 84.5 for <529,000 mg, 20.6 for 529,000-1,007,799 mg, and 6.3 for >1,007,799 mg; 86.3 for <1085 days, 20.3 for 1085-2094 days, and 4.7 for >2094 days for duration of therapy. The hazard ratio for thyroid cancer decreased significantly in metformin users as a function of dose and duration of metformin therapy. Conclusions: Metformin appears to be associated with a preventive effect on thyroid cancer development in a nationwide population-based study, but is not effective in the early phase of treatment. Considering the increasing prevalence of obesity and the role of insulin resistance in the development of cancer, metformin might be the preferred treatment for its dual anti-diabetic and antitumor effects.",
author = "Cho, {Yoon Young} and Kang, {Min Jin} and Kim, {Soo Kyoung} and Jung, {Jung Hwa} and Hahm, {Jong Ryeal} and Kim, {Tae Hyuk} and Nam, {Joo Young} and byungwan lee and Lee, {Yong Ho} and Chung, {Jae Hoon} and Song, {Sun Ok} and Kim, {Sun Wook}",
year = "2018",
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Cho, YY, Kang, MJ, Kim, SK, Jung, JH, Hahm, JR, Kim, TH, Nam, JY, lee, B, Lee, YH, Chung, JH, Song, SO & Kim, SW 2018, 'Protective Effect of Metformin Against Thyroid Cancer Development: A Population-Based Study in Korea', Thyroid, vol. 28, no. 7, pp. 864-870. https://doi.org/10.1089/thy.2017.0550

Protective Effect of Metformin Against Thyroid Cancer Development : A Population-Based Study in Korea. / Cho, Yoon Young; Kang, Min Jin; Kim, Soo Kyoung; Jung, Jung Hwa; Hahm, Jong Ryeal; Kim, Tae Hyuk; Nam, Joo Young; lee, byungwan; Lee, Yong Ho; Chung, Jae Hoon; Song, Sun Ok; Kim, Sun Wook.

In: Thyroid, Vol. 28, No. 7, 01.07.2018, p. 864-870.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Protective Effect of Metformin Against Thyroid Cancer Development

T2 - A Population-Based Study in Korea

AU - Cho, Yoon Young

AU - Kang, Min Jin

AU - Kim, Soo Kyoung

AU - Jung, Jung Hwa

AU - Hahm, Jong Ryeal

AU - Kim, Tae Hyuk

AU - Nam, Joo Young

AU - lee, byungwan

AU - Lee, Yong Ho

AU - Chung, Jae Hoon

AU - Song, Sun Ok

AU - Kim, Sun Wook

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Background: Metformin, the most widely used drug for type 2 diabetes, has recently attracted attention with regard to its antitumor activity. However, clinical studies have yielded conflicting results regarding the association between metformin and thyroid cancer development, despite its antitumor effect in preclinical studies. Methods: This is a retrospective cohort study using the Korean National Health Insurance claim database. Matched populations of 128,453 metformin users and 128,453 non-users were analyzed for thyroid cancer incidence. Metformin users were categorized into lowest, middle, and highest tertiles according to cumulative dose or duration of metformin therapy. Results: Thyroid cancer developed in 340 (0.26%) metformin users and 487 (0.38%) non-users during a mean follow-up of 7.2 years (hazard ratio = 0.69 [confidence interval 0.60-0.79]; p < 0.001). The incidence of thyroid cancer per 10 5 person-years was 51.6 in metformin non-users. For metformin users, the incidence was 84.5 for <529,000 mg, 20.6 for 529,000-1,007,799 mg, and 6.3 for >1,007,799 mg; 86.3 for <1085 days, 20.3 for 1085-2094 days, and 4.7 for >2094 days for duration of therapy. The hazard ratio for thyroid cancer decreased significantly in metformin users as a function of dose and duration of metformin therapy. Conclusions: Metformin appears to be associated with a preventive effect on thyroid cancer development in a nationwide population-based study, but is not effective in the early phase of treatment. Considering the increasing prevalence of obesity and the role of insulin resistance in the development of cancer, metformin might be the preferred treatment for its dual anti-diabetic and antitumor effects.

AB - Background: Metformin, the most widely used drug for type 2 diabetes, has recently attracted attention with regard to its antitumor activity. However, clinical studies have yielded conflicting results regarding the association between metformin and thyroid cancer development, despite its antitumor effect in preclinical studies. Methods: This is a retrospective cohort study using the Korean National Health Insurance claim database. Matched populations of 128,453 metformin users and 128,453 non-users were analyzed for thyroid cancer incidence. Metformin users were categorized into lowest, middle, and highest tertiles according to cumulative dose or duration of metformin therapy. Results: Thyroid cancer developed in 340 (0.26%) metformin users and 487 (0.38%) non-users during a mean follow-up of 7.2 years (hazard ratio = 0.69 [confidence interval 0.60-0.79]; p < 0.001). The incidence of thyroid cancer per 10 5 person-years was 51.6 in metformin non-users. For metformin users, the incidence was 84.5 for <529,000 mg, 20.6 for 529,000-1,007,799 mg, and 6.3 for >1,007,799 mg; 86.3 for <1085 days, 20.3 for 1085-2094 days, and 4.7 for >2094 days for duration of therapy. The hazard ratio for thyroid cancer decreased significantly in metformin users as a function of dose and duration of metformin therapy. Conclusions: Metformin appears to be associated with a preventive effect on thyroid cancer development in a nationwide population-based study, but is not effective in the early phase of treatment. Considering the increasing prevalence of obesity and the role of insulin resistance in the development of cancer, metformin might be the preferred treatment for its dual anti-diabetic and antitumor effects.

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