Metformin therapy reduces the risk of malignancy after heart transplantation

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

doi:10.1016/j.healun.2017.06.009

Cited by 15 publications

(14 citation statements)

References 41 publications

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“…However, in the subgroup analysis of heart transplant recipients, there was a statistically significant reduction in malignancy at 15 years in the DMM arm. This finding supports that of Peled et al, 10 which found a significant malignancy risk reduction with use of metformin in a cohort of heart transplant recipients. The reduction in malignancy in this study is smaller in magnitude than described by Peled et al; however, Peled et al had a larger population of heart transplant recipients.…”

Section: Discussionsupporting

confidence: 91%

“…However, in this study, use of metformin did not impact risk of malignancy development in the multivariable analysis, and similarly, duration of therapy >3 years did not change the outcome. Other risk factors for malignancy identified in the literature were described in the baseline characteristics, including but not limited to older age, male sex, Caucasian race, tobacco use, EBV serostatus, and use of lymphocyte‐depleting agents 4,10,14,15 . The majority of these risk factors were well balanced between the two arms; however, use of lymphocyte‐depleting agents was significantly higher in the DMO arm, driven by the rate of rATG for induction.…”

Section: Discussionmentioning

confidence: 99%

“…A registry analysis of kidney transplant recipients between 2007 and 2013 found that only 4.7% of patients had been prescribed metformin within the first year post‐transplant despite metformin use being associated with a reduction in all‐cause mortality, including malignancy‐related death, as well as all‐cause graft failure 9 . A recent publication reported that use of metformin in heart transplant recipients was associated with a 90% reduction in risk of malignancy in their diabetic population 10 . The aim of the present study is to supplement the literature cited above by analyzing differences in malignancy rates in kidney, liver, and heart transplant recipients with diabetes at a large transplant center.…”

Section: Introductionmentioning

confidence: 99%

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Impact of metformin on malignancy in solid organ transplantation

Bartlett

January

Pottebaum

et al. 2020

Clinical Transplantation

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Malignancy after solid organ transplant is a common occurrence that is associated with increased morbidity and mortality. Literature in the general diabetic population has identified possible antineoplastic properties of metformin. This retrospective study aims to determine if metformin results in a malignancy risk reduction in a cohort of diabetic kidney, liver, and heart transplant recipients. The population included transplant recipients without use of metformin at any time point (DMO arm, n = 147) and those with use of metformin (DMM arm, n = 172); the two arms were matched based on organ type and transplant date prior to application of exclusion criteria. Recipients with prior malignancy, malignancy before diabetes diagnosis, and metformin duration <30 days were excluded. The primary endpoint of malignancy first occurrence post‐transplant was not found to be statistically significant at 1, 5, 10, and 15 years. In the subgroup of heart transplant recipients, there was a significant reduction in malignancy at 15 years post‐transplant. Older age and Caucasian race were identified as significant risk factors for malignancy, while never smoker was a protective factor. Metformin use in this solid organ transplant cohort was not found to significantly reduce malignancy risk compared to use of other anti‐diabetic agents.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impact of metformin on malignancy in solid organ transplantation

Bartlett

January

Pottebaum

et al. 2020

Clinical Transplantation

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“…A recently published study from Israel [41] prospectively following up diabetic patients after heart transplantions from 1994 to 2018 showed that metformin therapy was independently associated with a significant 90% reduction (95% CI: 0.02-0.46, p = 0.003) in the risk for the development of cardiac allograft vasculopathy (CAV), and a 91% reduction (95% CI: 0.02-0.42; p = 0.003) in the risk for CAV or cardiovascular mortality. The same group [42] previously reported that diabetic patients 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 heart transplantation as compared with non-DM patients.…”

Section: Metformin Improves Prognosis After Kidney and Heart Transplamentioning

confidence: 57%

The right place for metformin today

Schernthaner

2020

Diabetes Research and Clinical Practice

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“…In a small case series of patients who were followed-up after heart transplantation, only 4% of the T2D patients developed cancer in contrast to 62% of T2D patients who were not treated with MTF and 27% who were not T2D patients [ 153 ]. Two out of five diagnosed cancers were hematological malignancies in the T2D patient group receiving MTF, whereas skin cancer was most prevalent in the two other groups.…”

Section: Mtf Effects On Cancer: Population-based Studies Clinicalmentioning

confidence: 99%

Pleiotropic Effects of Metformin on Cancer

Schulten

2018

IJMS

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Metformin (MTF) is a natural compound derived from the legume Galega officinalis. It is the first line antidiabetic drug for type 2 diabetes (T2D) treatment. One of its main antidiabetic effects results from the reduction of hepatic glucose release. First scientific evidence for the anticancer effects of MTF was found in animal research, published in 2001, and some years later a retrospective observational study provided evidence that linked MTF to reduced cancer risk in T2D patients. Its pleiotropic anticancer effects were studied in numerous in vitro and in vivo studies at the molecular and cellular level. Although the majority of these studies demonstrated that MTF is associated with certain anticancer properties, clinical studies and trials provided a mixed view on its beneficial anticancer effects. This review emphasizes the pleiotropic effects of MTF and recent progress made in MTF applications in basic, preclinical, and clinical cancer research.

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Metformin therapy reduces the risk of malignancy after heart transplantation

Cited by 15 publications

References 41 publications

Impact of metformin on malignancy in solid organ transplantation

Impact of metformin on malignancy in solid organ transplantation

The right place for metformin today

Pleiotropic Effects of Metformin on Cancer

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