Huang-Lucas, Claire

Koutroumpakis, Efstratios

Taegtmeyer, Heinrich

English

DigitalCommons@The Texas Medical Center

Cardiology. 2023 Dec; 148(6): 545–546.Published online 2023 Sep 6. doi: 10.1159/000533995: 10.1159/000533995PMCID: PMC10733930PMID: 37673051More on the Magic of MetforminEfstratios Koutroumpakis, Claire Huang-Lucas, and Heinrich TaegtmeyerDepartment of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADivision of Cardiovascular Medicine, Department of Internal Medicine, McGovern Medical School at UTHealth, TheUniversity of Texas Health Science Center at Houston, Houston, TX, USACorresponding author.Correspondence to: Heinrich Taegtmeyer, heinrich.taegtmeyer@uth.tmc.eduReceived 2023 Aug 31; Accepted 2023 Aug 31.Copyright © 2023 The Author(s). Published by S. Karger AG, BaselThis article is licensed under the Creative Commons Attribution 4.0 International License (CC BY)(http://www.karger.com/Services/OpenAccessLicense). Usage, derivative works and distribution are permitted providedthat proper credit is given to the author and the original publisher.Dear editor,We read with interest the narrative review on “Cardiovascular Protection by Metformin: LatestAdvances in Basic and Clinical Research” by Li and Li [1] and agree with the authors’ main conclu-sion. Further preclinical studies and large-scale randomized clinical trials are needed to elucidatemetformin’s action on the cardiovascular system.Over the last decade, we have made the following observations: (1) Metformin is safe and effectivein diabetic patients with heart failure [2]. (2) The dual action of metformin on the liver (inhibitinggluconeogenesis) and the heart (activating AMP kinase) contributes to the unlocking of the failingheart from metabolic stress [3]. (3) In the inotropically stimulated isolated working rat heart stud-ied ex vivo, prior metformin treatment in vivo, couples glucose uptake and oxidation and improvescontractile function most likely by activating AMP kinase [4]. (4) Those initial observations havesubsequently been extended to a model of pressure-induced cardiac stress, where metformin im-proves cardiac glucose metabolism and function, and where metformin prevents left ventricularhypertrophy in spontaneously hypertensive rats [5]. Lastly, and perhaps most importantly, is thecytostatic action of metformin [6, 7], most likely targeting metabolic mechanisms similar to thosedescribed in cardiac hypertrophy. In other words, the stressed heart hypertrophies and fails, whilethe stressed cancer cells hypertrophy and divide. We note that heart muscle cells are postmitotic a  b  baband do not divide, while the opposite is true for cancer cells. Our line of reasoning would thenmake metformin an attractive agent which protects the heart and kills the cancer. This, we wouldlike to reason, is the magic of metformin. More work is needed, and the horizon seems endless.Conflict of Interest StatementThe authors have no relevant  inancial or non- inancial con licts of interest to disclose.Funding SourcesThis study was supported by a grant from the National Institutes of Health to H.T. (R01-HL61483).Author ContributionsE.K. and C.H.L. contributed to the review of the literature and writing of the letter. H.T. contributedto the conception of the idea, review of the literature, and writing of the letter.Funding StatementThis study was supported by a grant from the National Institutes of Health to H.T. (R01-HL61483).References1. Li JZ, Li YR. Cardiovascular protection by metformin: latest advances in basic and clinical Research. Cardiology.2023;148(4):374–84. 10.1159/000531432. [PubMed: 37307806] [CrossRef: 10.1159/000531432]2. Ekeruo IA, Solhpour A, Taegtmeyer H. Metformin in diabetic patients with heart failure: safe and effective? Curr	CardiovascRisk	Rep. 2013 Dec 1;7(6):417–22. 10.1007/s12170-013-0355-4. [PMCID: PMC3899937] [PubMed: 24466358] [CrossRef:10.1007/s12170-013-0355-4]3. Koutroumpakis E, Jozwik B, Aguilar D, Taegtmeyer H. Strategies of unloading the failing heart from metabolic stress. Am	JMed. 2020 Mar;133(3):290–6. 10.1016/j.amjmed.2019.08.035. [PMCID: PMC7054139] [PubMed: 31520618] [CrossRef:10.1016/j.amjmed.2019.08.035]4. Sen S, Kundu BK, Wu HC, Hashmi SS, Guthrie P, Locke LW, et al.. Glucose regulation of load-induced mTOR signaling andER stress in mammalian heart. J	Am	Heart	Assoc. 2013 May 17;2(3):e004796. 10.1161/JAHA.113.004796. [PMCID:PMC3698799] [PubMed: 23686371] [CrossRef: 10.1161/JAHA.113.004796]5. Li J, Minćzuk K, Massey JC, Howell NL, Roy RJ, Paul S, et al.. Metformin improves cardiac metabolism and function, andprevents left ventricular hypertrophy in spontaneously hypertensive rats. J	Am	Heart	Assoc. 2020 Apr 7;9(7):e015154.10.1161/JAHA.119.015154. [PMCID: PMC7428616] [PubMed: 32248762] [CrossRef: 10.1161/JAHA.119.015154]6. Vancura A, Bu P, Bhagwat M, Zeng J, Vancurova I. Metformin as an anticancer agent. Trends	Pharmacol	Sci. 2018Oct;39(10):867–78. 10.1016/j.tips.2018.07.006. [PMCID: PMC6153060] [PubMed: 30150001] [CrossRef:10.1016/j.tips.2018.07.006]7. Zaidi S, Gandhi J, Joshi G, Smith NL, Khan SA. The anticancer potential of metformin on prostate cancer. Prostate	CancerProstatic	Dis. 2019 Sep;22(3):351–61. 10.1038/s41391-018-0085-2. [PubMed: 30651580] [CrossRef: 10.1038/s41391-018-0085-2]

More on the Magic of Metformin

https://digitalcommons.library.tmc.edu/cgi/viewcontent.cgi?article=1593&context=uthmed_docs

More on the Magic of Metformin

Abstract

Similar works

Full text

Available Versions

DigitalCommons@The Texas Medical Center