Metformin therapy reduces the risk of malignancy after heart transplantation

Yael Peled, Jacob Lavee, Eugenia Raichlin, Moshe Katz, Michael Arad, Yigal Kassif, Amir Peled, Elad Asher, Dan Elian, Yedael Har-Zahav, Nir Shlomo, Dov Freimark, Ilan Goldenberg, Robert Klempfner

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Abstract

Background Malignancy and diabetes mellitus (DM) cause significant morbidity and mortality after heart transplantation (HTx). Metformin, one of the most commonly used anti-diabetic drugs worldwide, has also been shown to exhibit anti-tumor activity. We therefore investigated the association between metformin therapy and malignancy after HTx. Methods The study population comprised 237 patients who underwent HTx between 1991 and 2016 and were prospectively followed-up. Clinical data were recorded on prospectively designed forms. The primary outcome was any cancer recorded during 15 years of follow-up. Treatment with metformin and the development of DM after HTx were assessed as time-dependent factors in the analyses. Results Of the 237 study patients, 85 (36%) had diabetes. Of the DM patients, 48 (56%) were treated with metformin. Kaplan–Meier survival analysis showed that, at 15 years after HTx, malignancy rate was 4% for DM patients treated with metformin, 62% for those who did not receive metformin and 27% for non-DM patients (log-rank test, p < 0.0001). Consistently, multivariate analysis showed that for DM patients, metformin therapy was independently associated with a significant 90% reduction (hazard ratio = 0.10; 95% confidence interval 0.02 to 0.40; p = 0.001) in the risk of the development of a malignancy. DM patients who were treated with metformin had a markedly lower risk (65%; p = 0.001) for the development of a malignancy or death after HTx as compared with non-DM patients. Conclusions Our findings suggest that metformin therapy is independently associated with a significant reduction in the risk of malignancy after HTx.

Original languageEnglish (US)
Pages (from-to)1350-1357
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume36
Issue number12
DOIs
StatePublished - Dec 2017

Fingerprint

Metformin
Heart Transplantation
Diabetes Mellitus
Neoplasms
Therapeutics
Risk Reduction Behavior
Survival Analysis
Statistical Factor Analysis
Multivariate Analysis
Confidence Intervals
Morbidity
Mortality

Keywords

  • diabetes mellitus
  • heart transplantation
  • malignancy
  • metformin
  • reduction

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

Peled, Y., Lavee, J., Raichlin, E., Katz, M., Arad, M., Kassif, Y., ... Klempfner, R. (2017). Metformin therapy reduces the risk of malignancy after heart transplantation. Journal of Heart and Lung Transplantation, 36(12), 1350-1357. https://doi.org/10.1016/j.healun.2017.06.009

Metformin therapy reduces the risk of malignancy after heart transplantation. / Peled, Yael; Lavee, Jacob; Raichlin, Eugenia; Katz, Moshe; Arad, Michael; Kassif, Yigal; Peled, Amir; Asher, Elad; Elian, Dan; Har-Zahav, Yedael; Shlomo, Nir; Freimark, Dov; Goldenberg, Ilan; Klempfner, Robert.

In: Journal of Heart and Lung Transplantation, Vol. 36, No. 12, 12.2017, p. 1350-1357.

Research output: Contribution to journalArticle

Peled, Y, Lavee, J, Raichlin, E, Katz, M, Arad, M, Kassif, Y, Peled, A, Asher, E, Elian, D, Har-Zahav, Y, Shlomo, N, Freimark, D, Goldenberg, I & Klempfner, R 2017, 'Metformin therapy reduces the risk of malignancy after heart transplantation', Journal of Heart and Lung Transplantation, vol. 36, no. 12, pp. 1350-1357. https://doi.org/10.1016/j.healun.2017.06.009
Peled, Yael ; Lavee, Jacob ; Raichlin, Eugenia ; Katz, Moshe ; Arad, Michael ; Kassif, Yigal ; Peled, Amir ; Asher, Elad ; Elian, Dan ; Har-Zahav, Yedael ; Shlomo, Nir ; Freimark, Dov ; Goldenberg, Ilan ; Klempfner, Robert. / Metformin therapy reduces the risk of malignancy after heart transplantation. In: Journal of Heart and Lung Transplantation. 2017 ; Vol. 36, No. 12. pp. 1350-1357.
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abstract = "Background Malignancy and diabetes mellitus (DM) cause significant morbidity and mortality after heart transplantation (HTx). Metformin, one of the most commonly used anti-diabetic drugs worldwide, has also been shown to exhibit anti-tumor activity. We therefore investigated the association between metformin therapy and malignancy after HTx. Methods The study population comprised 237 patients who underwent HTx between 1991 and 2016 and were prospectively followed-up. Clinical data were recorded on prospectively designed forms. The primary outcome was any cancer recorded during 15 years of follow-up. Treatment with metformin and the development of DM after HTx were assessed as time-dependent factors in the analyses. Results Of the 237 study patients, 85 (36{\%}) had diabetes. Of the DM patients, 48 (56{\%}) were treated with metformin. Kaplan–Meier survival analysis showed that, at 15 years after HTx, malignancy rate was 4{\%} for DM patients treated with metformin, 62{\%} for those who did not receive metformin and 27{\%} for non-DM patients (log-rank test, p < 0.0001). Consistently, multivariate analysis showed that for DM patients, metformin therapy was independently associated with a significant 90{\%} reduction (hazard ratio = 0.10; 95{\%} confidence interval 0.02 to 0.40; p = 0.001) in the risk of the development of a malignancy. DM patients who were treated with metformin had a markedly lower risk (65{\%}; p = 0.001) for the development of a malignancy or death after HTx as compared with non-DM patients. Conclusions Our findings suggest that metformin therapy is independently associated with a significant reduction in the risk of malignancy after HTx.",
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T1 - Metformin therapy reduces the risk of malignancy after heart transplantation

AU - Peled, Yael

AU - Lavee, Jacob

AU - Raichlin, Eugenia

AU - Katz, Moshe

AU - Arad, Michael

AU - Kassif, Yigal

AU - Peled, Amir

AU - Asher, Elad

AU - Elian, Dan

AU - Har-Zahav, Yedael

AU - Shlomo, Nir

AU - Freimark, Dov

AU - Goldenberg, Ilan

AU - Klempfner, Robert

PY - 2017/12

Y1 - 2017/12

N2 - Background Malignancy and diabetes mellitus (DM) cause significant morbidity and mortality after heart transplantation (HTx). Metformin, one of the most commonly used anti-diabetic drugs worldwide, has also been shown to exhibit anti-tumor activity. We therefore investigated the association between metformin therapy and malignancy after HTx. Methods The study population comprised 237 patients who underwent HTx between 1991 and 2016 and were prospectively followed-up. Clinical data were recorded on prospectively designed forms. The primary outcome was any cancer recorded during 15 years of follow-up. Treatment with metformin and the development of DM after HTx were assessed as time-dependent factors in the analyses. Results Of the 237 study patients, 85 (36%) had diabetes. Of the DM patients, 48 (56%) were treated with metformin. Kaplan–Meier survival analysis showed that, at 15 years after HTx, malignancy rate was 4% for DM patients treated with metformin, 62% for those who did not receive metformin and 27% for non-DM patients (log-rank test, p < 0.0001). Consistently, multivariate analysis showed that for DM patients, metformin therapy was independently associated with a significant 90% reduction (hazard ratio = 0.10; 95% confidence interval 0.02 to 0.40; p = 0.001) in the risk of the development of a malignancy. DM patients who were treated with metformin had a markedly lower risk (65%; p = 0.001) for the development of a malignancy or death after HTx as compared with non-DM patients. Conclusions Our findings suggest that metformin therapy is independently associated with a significant reduction in the risk of malignancy after HTx.

AB - Background Malignancy and diabetes mellitus (DM) cause significant morbidity and mortality after heart transplantation (HTx). Metformin, one of the most commonly used anti-diabetic drugs worldwide, has also been shown to exhibit anti-tumor activity. We therefore investigated the association between metformin therapy and malignancy after HTx. Methods The study population comprised 237 patients who underwent HTx between 1991 and 2016 and were prospectively followed-up. Clinical data were recorded on prospectively designed forms. The primary outcome was any cancer recorded during 15 years of follow-up. Treatment with metformin and the development of DM after HTx were assessed as time-dependent factors in the analyses. Results Of the 237 study patients, 85 (36%) had diabetes. Of the DM patients, 48 (56%) were treated with metformin. Kaplan–Meier survival analysis showed that, at 15 years after HTx, malignancy rate was 4% for DM patients treated with metformin, 62% for those who did not receive metformin and 27% for non-DM patients (log-rank test, p < 0.0001). Consistently, multivariate analysis showed that for DM patients, metformin therapy was independently associated with a significant 90% reduction (hazard ratio = 0.10; 95% confidence interval 0.02 to 0.40; p = 0.001) in the risk of the development of a malignancy. DM patients who were treated with metformin had a markedly lower risk (65%; p = 0.001) for the development of a malignancy or death after HTx as compared with non-DM patients. Conclusions Our findings suggest that metformin therapy is independently associated with a significant reduction in the risk of malignancy after HTx.

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