• 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, and Robert Klempfner.
• The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: Yael.Peled-Potashnik@sheba.health.gov.il.
• J. Heart Lung Transplant. 2017 Dec 1; 36 (12): 1350-1357.

BackgroundMalignancy 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.MethodsThe 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.ResultsOf 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.ConclusionsOur findings suggest that metformin therapy is independently associated with a significant reduction in the risk of malignancy after HTx.Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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