Metformin pathways: pharmacokinetics and pharmacodynamics

Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action

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Diabetes and Cancer

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Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain

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The LKB1-AMPK pathway: metabolism and growth control in tumour suppression

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Cellular and molecular mechanisms of metformin: an overview

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Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I

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Efficacy of Metformin in Patients with Non-Insulin-Dependent Diabetes Mellitus

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Clinical pharmacokinetics of metformin

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Metformin Inhibits Hepatic Gluconeogenesis in Mice Independently of the LKB1/AMPK Pathway via a Decrease in Hepatic Energy State

Foretz, M., Hébrard, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., Sakamoto, K., Andreelli, F., & Viollet, B. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40671 · Cited by 1,181 · see citing works

Mechanism by which metformin reduces glucose production in type 2 diabetes.

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Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action

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The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level

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A human transporter protein that mediates the final excretion step for toxic organic cations

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Effect of Genetic Variation in the Organic Cation Transporter 1, OCT1, on Metformin Pharmacokinetics

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Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes

The GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group (2010) · Nature Genetics · doi:10.1038/ng.735 · Cited by 448 · see citing works

Mechanism for Fatty Acid “Sparing” Effect on Glucose-induced Transcription

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Metformin Inhibits Hepatic Gluconeogenesis Through AMP-Activated Protein Kinase–Dependent Regulation of the Orphan Nuclear Receptor SHP

Kim, Y. D., Park, K.-G., Lee, Y.-S., Park, Y.-Y., Kim, D.-K., Nedumaran, B., Jang, W. G., Cho, W.-J., Ha, J., Lee, I.-K., et al. (2008) · Diabetes · doi:10.2337/db07-0381 · Cited by 422 · see citing works

Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H+-organic cation antiporters

Tanihara, Y., Masuda, S., Sato, T., et al. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.04.010 · Cited by 419 · see citing works

AMP-Activated Protein Kinase as a Drug Target

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Expression of Organic Cation Transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) Is Affected by Genetic Factors and Cholestasis in Human Liver†

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Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review

Natali, A., & Ferrannini, E. (2006) · Diabetologia · doi:10.1007/s00125-006-0141-7 · Cited by 377 · see citing works

Organic Cation Transporters (OCTs, MATEs), In Vitro and In Vivo Evidence for the Importance in Drug Therapy

Nies, A. T., Koepsell, H., Damme, K., & Schwab, M. G. (2010) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-14541-4_3 · Cited by 373 · see citing works

The Effects of Genetic Polymorphisms in the Organic Cation Transporters OCT1, OCT2, and OCT3 on the Renal Clearance of Metformin

Tzvetkov, M. V., Vormfelde, S. V., Balen, D., Meineke, I., Schmidt, T., Sehrt, D. B., Sabolić, I., Koepsell, H., & Brockmöller, J. (2009) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2009.92 · Cited by 349 · see citing works

Metformin therapy and clinical uses

Scarpello, J. H., & Howlett, H. C. (2008) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2008.027 · Cited by 318 · see citing works

Genetic Variation in the Multidrug and Toxin Extrusion 1 Transporter Protein Influences the Glucose-Lowering Effect of Metformin in Patients With Diabetes: A Preliminary Study

Becker, M. L., Visser, L. E., van Schaik, R. H. N., Albert Hofman, D., Uitterlinden, A. G., & Stricker, B. H. C. (2009) · Diabetes · doi:10.2337/db08-1028 · Cited by 291 · see citing works

OCT2 polymorphisms and in-vivo renal functional consequence: studies with metformin and cimetidine

Wang, Z., Yin, O. Q. P., Tomlinson, B., et al. (2008) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328302cd41 · Cited by 281 · see citing works

Reduction of metformin renal tubular secretion by cimetidine in man.

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Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the Diabetes Prevention Program

Jablonski, K. A., McAteer, J. B., de Bakker, P. I. W., Franks, P. W., Pollin, T. I., Hanson, R. L., Saxena, R., Fowler, S., Shuldiner, A. R., Knowler, W. C., et al. (2010) · Diabetes · doi:10.2337/db10-0543 · Cited by 271 · see citing works

Genetic Variants of the Organic Cation Transporter 2 Influence the Disposition of Metformin

Song, I., Hj, S., Shim, E., Jung, I., Kim, W., Shon, J. H., & Shin, J.-G. (2008) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2008.61 · Cited by 268 · see citing works

Drug specificity and intestinal membrane localization of human organic cation transporters (OCT).

Müller, J., Lips, K., Metzner, L., Neubert, R., Koepsell, H., & Brandsch, M. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.09.011 · Cited by 268 · see citing works

The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c

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Metformin Transport by a Newly Cloned Proton-Stimulated Organic Cation Transporter (Plasma Membrane Monoamine Transporter) Expressed in Human Intestine

Zhou, M., Li, X., & Wang, J. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.015495 · Cited by 251 · see citing works

The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells

Vazquez-Martin, A., Oliveras-Ferraros, C., & Menendez, J. A. (2009) · Cell Cycle · doi:10.4161/cc.8.1.7499 · Cited by 250 · see citing works

Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin

Chen, Y., Li, S., Brown, C., Cheatham, S. C., Castro, R. A., Leabman, M. K., Urban, T. J., Chen, L., Yee, S. W., Choi, J. H., et al. (2009) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32832cc7e9 · Cited by 249 · see citing works

Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1

Zhuang, Y., & Miskimins, W. K. (2008) · Journal of Molecular Signaling · doi:10.1186/1750-2187-3-18 · Cited by 247 · see citing works

Effects of a MATE Protein Inhibitor, Pyrimethamine, on the Renal Elimination of Metformin at Oral Microdose and at Therapeutic Dose in Healthy Subjects

Kusuhara, H., Ito, S., Kumagai, Y., Jiang, M., Shiroshita, T., Moriyama, Y., Inoue, K., Yuasa, H., & Sugiyama, Y. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.36 · Cited by 216 · see citing works

Competitive Inhibition of the Luminal Efflux by Multidrug and Toxin Extrusions, but Not Basolateral Uptake by Organic Cation Transporter 2, Is the Likely Mechanism Underlying the Pharmacokinetic Drug-Drug Interactions Caused by Cimetidine in the Kidney

Ito, S., Kusuhara, H., Yokochi, M., et al. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.184986 · Cited by 212 · see citing works

Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin

Shikata, E., Yamamoto, R., Takane, H., Shigemasa, C., Ikeda, T., Otsubo, K., & Ieiri, I. (2006) · Journal of Human Genetics · doi:10.1007/s10038-006-0087-0 · Cited by 207 · see citing works

Role of Organic Cation Transporter 3 (SLC22A3) and Its Missense Variants in the Pharmacologic Action of Metformin

Chen, L., Pawlikowski, B., Schlessinger, A., More, S. S., Stryke, D., Johns, S., Portman, M., Chen, E., Ferrin, T., Sali, A., et al. (2010) · Pharmacogenetics & Genomics · doi:10.1097/fpc.0b013e32833fe789 · Cited by 203 · see citing works

Interactions of Tyrosine Kinase Inhibitors with Organic Cation Transporters and Multidrug and Toxic Compound Extrusion Proteins

Minematsu, T., & Giacomini, K. M. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0731 · Cited by 196 · see citing works

Involvement of Human Multidrug and Toxin Extrusion 1 in the Drug Interaction between Cimetidine and Metformin in Renal Epithelial Cells

Tsuda, M., Terada, T., Ueba, M., Sato, T., Masuda, S., Katsura, T., & Inui, K. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.147918 · Cited by 194 · see citing works

Reduced-Function SLC22A1 Polymorphisms Encoding Organic Cation Transporter 1 and Glycemic Response to Metformin: A GoDARTS Study

Zhou, K., Donnelly, L. A., Kimber, C. H., Donnan, P. T., Doney, A. S. F., Leese, G., Hattersley, A. T., McCarthy, M. I., Morris, A. D., Palmer, C. N. A., et al. (2009) · Diabetes · doi:10.2337/db08-0896 · Cited by 187 · see citing works

Proton Pump Inhibitors Inhibit Metformin Uptake by Organic Cation Transporters (OCTs)

Nies, A. T., Hofmann, U., Resch, C., Schaeffeler, E., Rius, M., & Schwab, M. G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022163 · Cited by 184 · see citing works

Targeted Disruption of the Multidrug and Toxin Extrusion 1 (Mate1) Gene in Mice Reduces Renal Secretion of Metformin

Tsuda, M., Terada, T., Mizuno, T., Katsura, T., Shimakura, J., & Inui, K. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.056242 · Cited by 173 · see citing works

A Common 5′-UTR Variant in MATE2-K Is Associated With Poor Response to Metformin

Choi, J. H., Yee, S. W., Ramirez, A. H., Morrissey, K. M., Jang, G. H., Joski, P. J., Mefford, J., Hesselson, S., Schlessinger, A., Jenkins, G. P., et al. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.165 · Cited by 156 · see citing works

Potent and Specific Inhibition of mMate1-Mediated Efflux of Type I Organic Cations in the Liver and Kidney by Pyrimethamine

Ito, S., Kusuhara, H., Kuroiwa, Y., Wu, C., Moriyama, Y., Inoue, K., Kondo, T., Yuasa, H., Nakayama, H., Horita, S., et al. (2010) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.163642 · Cited by 153 · see citing works

Polymorphism in Human Organic Cation Transporters and Metformin Action

Takane, H., Shikata, E., Otsubo, K., Higuchi, S., & Ieiri, I. (2008) · Pharmacogenomics · doi:10.2217/14622416.9.4.415 · Cited by 140 · see citing works

Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response

Becker, M. L., Visser, L. E., van Schaik, R. H. N., Albert Hofman, D., Uitterlinden, A. G., & Stricker, B. H. C. (2009) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328333bb11 · Cited by 139 · see citing works

Interaction of Oral Antidiabetic Drugs With Hepatic Uptake Transporters

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Regulation of hepatic metabolism by AMPK

Foretz, M., & Viollet, B. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.09.014 · Cited by 120 · see citing works

Neither LKB1 Nor AMPK Are the Direct Targets of Metformin

Hardie, D. G. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.07.032 · Cited by 111 · see citing works

Role of human placental apical membrane transporters in the efflux of glyburide, rosiglitazone, and metformin

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Ovulatory Response to Treatment of Polycystic Ovary Syndrome Is Associated with a Polymorphism in the STK11 Gene

Legro, R. S., Barnhart, H. X., Schlaff, W. D., Carr, B. R., Diamond, M. P., Carson, S. A., Steinkampf, M. P., Coutifaris, C., McGovern, P. G., Cataldo, N. A., et al. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1736 · Cited by 102 · see citing works

Transcellular transport of organic cations in double-transfected MDCK cells expressing human organic cation transporters hOCT1/hMATE1 and hOCT2/hMATE1

Sato, T., Masuda, S., Yonezawa, A., et al. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.07.005 · Cited by 101 · see citing works

Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene

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Pharmacogenetics of metformin response: a step in the path toward personalized medicine

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Membrane localization and pH-dependent transport of a newly cloned organic cation transporter (PMAT) in kidney cells

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The role of ATM in response to metformin treatment and activation of AMPK

Yee, S. W., Chen, L., & Giacomini, K. M. (2012) · Nature Genetics · doi:10.1038/ng.2236 · Cited by 55 · see citing works

Organic Cation Transporter 1 Polymorphisms Predict the Metabolic Response to Metformin in Women with the Polycystic Ovary Syndrome

Gambineri, A., Tomassoni, F., Gasparini, D. I., Rocco, A. D., Mantovani, V., Pagotto, U., Altieri, P., Sanna, S., Fulghesu, A. M., & Pasquali, R. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0145 · Cited by 53 · see citing works

Metformin and cancer: licence to heal?

Papanas, N., Maltezos, E., & Mikhailidis, D. P. (2010) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2010.499122 · Cited by 37 · see citing works

Serine racemase rs391300 G/A polymorphism influences the therapeutic efficacy of metformin in Chinese patients with diabetes mellitus type 2

Dong, M., Gong, Z., Dai, X., Lei, G., Lu, H., Fan, L., Qu, J., Zhou, H., & Liu, Z. (2011) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2011.05610.x · Cited by 23 · see citing works

Is Pharmacogenomics our Future? Metformin, Ovulation and Polymorphism of the STK11 Gene in Polycystic Ovary Syndrome

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Metformin: from mechanisms of action to therapies

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Benefits of Metformin in Attenuating the Hallmarks of Aging

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Metformin Action: Concentrations Matter

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Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review

Crowley, M. J., Diamantidis, C. J., McDuffie, J. R., Cameron, C. B., Stanifer, J. W., Mock, C. K., Wang, X., Tang, S., Nagi, A., Kosinski, A. S., et al. (2017) · Annals of Internal Medicine · doi:10.7326/m16-1901 · Cited by 287 · see citing works

A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan

Mohammed, I., Hollenberg, M. D., Ding, H., & Triggle, C. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.718942 · Cited by 278 · see citing works

Metformin-induced mitochondrial Complex I inhibition: facts, uncertainties, and consequences

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Metformin: A Hopeful Promise in Aging Research

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Metformin and gut microbiota: their interactions and their impact on diabetes

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Endothelial Function and Dysfunction: Impact of Metformin

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Glyoxalase 1 Modulation in Obesity and Diabetes

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Metformin for treatment of fragile X syndrome and other neurological disorders

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The emerging role of metformin in gestational diabetes mellitus

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Metformin to treat Huntington disease: A pleiotropic drug against a multi-system disorder

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당뇨를 동반한 4기 대장암 환자에서 항암약물요법 반응 및 생존율에 대한 Metformin의 효과

이동준, 김번, 이진하, et al. (2012)

Cloning and Characterization of Rat BAT3 cDNA

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Metformin for Prevention of Type 2 Diabetes

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A Rare Side Effect of Metformin: Metformin-Induced Hepatotoxicity

Aksay, E. (2007) · DergiPark (Istanbul University) · Cited by 15 · see citing works

EFFECT OF THE NEMATODE PHASMARHABDITIS HERMAPHRODITA ON YOUNG STAGES OF THE PEST SLUG ARION LUSITANICUS

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