Study Summary
This trial is comparing the effects of metformin to a placebo in patients with advanced prostate cancer who are starting or have recently started ADT.
- Prostate Cancer
- Metabolic Syndrome
Video Summary
Treatment Effectiveness
Phase-Based Effectiveness
Study Objectives
1 Primary · 10 Secondary · Reporting Duration: Through study completion, an average of 3 years
Trial Safety
Phase-Based Safety
Side Effects for
Awards & Highlights
Trial Design
2 Treatment Groups
Metformin
1 of 2
Placebo
1 of 2
Experimental Treatment
Non-Treatment Group
300 Total Participants · 2 Treatment Groups
Primary Treatment: Metformin · Has Placebo Group · Phase 3
Trial Logistics
Trial Timeline
Who is running the clinical trial?
Eligibility Criteria
Age 18+ · Male Participants · 1 Total Inclusion Criteria
Mark “Yes” if the following statements are true for you:Who else is applying?
What state do they live in?
California | 50.0% |
North Carolina | 50.0% |
How old are they?
18 - 65 | 100.0% |
What portion of applicants met pre-screening criteria?
Did not meet criteria | 100.0% |
- Miettola, Juhani, Leo K. Niskanen, Heimo Viinamäki, Harri Sintonen, and Esko Kumpusalo. 2008. “Metabolic Syndrome Is Associated with Impaired Health-related Quality of Life: Lapinlahti 2005 Study”. Quality of Life Research. Springer Science and Business Media LLC. doi:10.1007/s11136-008-9386-6.
- James, Nicholas D, Matthew R Sydes, Noel W Clarke, Malcolm D Mason, David P Dearnaley, Melissa R Spears, Alastair W S Ritchie, et al.. 2016. “Addition of Docetaxel, Zoledronic Acid, or Both to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Survival Results from an Adaptive, Multiarm, Multistage, Platform Randomised Controlled Trial”. The Lancet. Elsevier BV. doi:10.1016/s0140-6736(15)01037-5.
- Reaven, Gerald M. 1988. “Role of Insulin Resistance in Human Disease”. Diabetes. American Diabetes Association. doi:10.2337/diab.37.12.1595.
- Haffner, Steven M, Rodolfo A Valdez, Helen P Hazuda, Braxton D Mitchell, Philip A Morales, and Michael P Stern. 1992. “Prospective Analysis of the Insulin-resistance Syndrome (syndrome X)”. Diabetes. American Diabetes Association. doi:10.2337/diab.41.6.715.
- Braga-Basaria, Milena, Adrian S. Dobs, Denis C. Muller, Michael A. Carducci, Majnu John, Josephine Egan, and Shehzad Basaria. 2006. “Metabolic Syndrome in Men with Prostate Cancer Undergoing Long-term Androgen-deprivation Therapy”. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). doi:10.1200/jco.2006.05.9741.
- Pollak, Michael N.. 2012. “Investigating Metformin for Cancer Prevention and Treatment: The End of the Beginning”. Cancer Discovery. American Association for Cancer Research (AACR). doi:10.1158/2159-8290.cd-12-0263.
- Malik, Shaista, Nathan D. Wong, Stanley S. Franklin, Tripthi V. Kamath, Gilbert J. L’Italien, Jose R. Pio, and G. Rhys Williams. 2004. “Impact of the Metabolic Syndrome on Mortality from Coronary Heart Disease, Cardiovascular Disease, and All Causes in United States Adults”. Circulation. Ovid Technologies (Wolters Kluwer Health). doi:10.1161/01.cir.0000140677.20606.0e.
- Park, Sang Shin, Yeong Sook Yoon, and Sang Woo Oh. 2011. “Health-related Quality of Life in Metabolic Syndrome: The Korea National Health and Nutrition Examination Survey 2005”. Diabetes Research and Clinical Practice. Elsevier BV. doi:10.1016/j.diabres.2010.11.010.
- Crook, Juanita M., Christopher J. O'Callaghan, Graeme Duncan, David P. Dearnaley, Celestia S. Higano, Eric M. Horwitz, Eliot Frymire, et al.. 2012. “Intermittent Androgen Suppression for Rising PSA Level After Radiotherapy”. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejmoa1201546.
- Lakka, Hanna-Maaria. 2002. “The Metabolic Syndrome and Total and Cardiovascular Disease Mortality in Middle-aged Men”. Jama. American Medical Association (AMA). doi:10.1001/jama.288.21.2709.
- Hussain, Maha, Catherine M. Tangen, Donna L. Berry, Celestia S. Higano, E. David Crawford, Glenn Liu, George Wilding, et al.. 2013. “Intermittent Versus Continuous Androgen Deprivation in Prostate Cancer”. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejmoa1212299.
- Solymoss, B.Charles, Martial G Bourassa, Lucien Campeau, Allan Sniderman, Michel Marcil, Jacques Lespérance, Sylvie Lévesque, and Susan Varga. 2004. “Effect of Increasing Metabolic Syndrome Score on Atherosclerotic Risk Profile and Coronary Artery Disease Angiographic Severity”. The American Journal of Cardiology. Elsevier BV. doi:10.1016/j.amjcard.2003.09.032.
- Tsai, H. K., A. V. D'Amico, N. Sadetsky, M.-H. Chen, and P. R. Carroll. 2007. “Androgen Deprivation Therapy for Localized Prostate Cancer and the Risk of Cardiovascular Mortality”. JNCI Journal of the National Cancer Institute. Oxford University Press (OUP). doi:10.1093/jnci/djm168.
- Cleffi, S., A.S. Neto, L.O. Reis, Priscila Maia, F. Fonseca, M.L. Wroclawski, M. Neves, et al.. 2011. “Terapia de privación de andrógenos y obesidad mórbida: ¿tienen en común el riesgo cardiovascular por síndrome metabólico?”. Actas urológicas españolas. Elsevier BV. doi:10.1016/j.acuro.2011.01.011.
- Morote, J., J. Ropero, J. Planas, A. Celma, J. Placer, R. Ferrer, and I. de Torres. 2014. “Síndrome metabólico en pacientes con cáncer de próstata sometidos a supresión androgénica”. Actas urológicas españolas. Elsevier BV. doi:10.1016/j.acuro.2013.09.008.
- Bosco, Cecilia, Danielle Crawley, Jan Adolfsson, Sarah Rudman, and Mieke Van Hemelrijck. 2015. “Quantifying the Evidence for the Risk of Metabolic Syndrome and Its Components Following Androgen Deprivation Therapy for Prostate Cancer: A Meta-analysis”. Edited by Zoran Culig. Plos One. Public Library of Science (PLoS). doi:10.1371/journal.pone.0117344.
- Segal, Roanne J., Robert D. Reid, Kerry S. Courneya, Shawn C. Malone, Matthew B. Parliament, Chris G. Scott, Peter M. Venner, et al.. 2003. “Resistance Exercise in Men Receiving Androgen Deprivation Therapy for Prostate Cancer”. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). doi:10.1200/jco.2003.09.534.
- Taylor, Cindy L. Carmack, Carl deMoor, Murray A. Smith, Andrea L. Dunn, Karen Basen-Engquist, Ingrid Nielsen, Curtis Pettaway, Rena Sellin, Pamela Massey, and Ellen R. Gritz. 2006. “active for Life After Cancer: A Randomized Trial Examining a Lifestyle Physical Activity Program for Prostate Cancer Patients”. Psycho-oncology. Wiley. doi:10.1002/pon.1023.
- Basaria, Shehzad, Denis C. Muller, Michael A. Carducci, Josephine Egan, and Adrian S. Dobs. 2006. “Hyperglycemia and Insulin Resistance in Men with Prostate Carcinoma Who Receive Androgen-deprivation Therapy”. Cancer. Wiley. doi:10.1002/cncr.21642.
- Tsai, Huei-Ting, Nancy L. Keating, Stephen K. Van Den Eeden, Reina Haque, Andrea E. Cassidy-Bushrow, Marianne Ulcickas Yood, Matthew R. Smith, and Arnold L. Potosky. 2015. “Risk of Diabetes Among Patients Receiving Primary Androgen Deprivation Therapy for Clinically Localized Prostate Cancer”. Journal of Urology. Ovid Technologies (Wolters Kluwer Health). doi:10.1016/j.juro.2014.12.027.
- Keating, Nancy L., Pang-Hsiang Liu, A. James O’Malley, Stephen J. Freedland, and Matthew R. Smith. 2014. “Androgen-deprivation Therapy and Diabetes Control Among Diabetic Men with Prostate Cancer”. European Urology. Elsevier BV. doi:10.1016/j.eururo.2013.02.023.
- Cox, Michael E., Martin E. Gleave, Mahvash Zakikhani, Robert H. Bell, Esther Piura, Elaine Vickers, Matthew Cunningham, Ola Larsson, Ladan Fazli, and Michael Pollak. 2009. “Insulin Receptor Expression by Human Prostate Cancers”. The Prostate. Wiley. doi:10.1002/pros.20852.
- Pollak, Michael. 2014. “Overcoming Drug Development Bottlenecks with Repurposing: Repurposing Biguanides to Target Energy Metabolism for Cancer Treatment”. Nature Medicine. Springer Science and Business Media LLC. doi:10.1038/nm.3596.
- Pollak, Michael. 2013. “Potential Applications for Biguanides in Oncology”. Journal of Clinical Investigation. American Society for Clinical Investigation. doi:10.1172/jci67232.
- Martin-Montalvo, Alejandro, Evi M. Mercken, Sarah J. Mitchell, Hector H. Palacios, Patricia L. Mote, Morten Scheibye-Knudsen, Ana P. Gomes, et al.. 2013. “Metformin Improves Healthspan and Lifespan in Mice”. Nature Communications. Springer Science and Business Media LLC. doi:10.1038/ncomms3192.
- Venkateswaran, V., A. Q. Haddad, N. E. Fleshner, R. Fan, L. M. Sugar, R. Nam, L. H. Klotz, and M. Pollak. 2007. “Association of Diet-induced Hyperinsulinemia with Accelerated Growth of Prostate Cancer (lncap) Xenografts”. JNCI Journal of the National Cancer Institute. Oxford University Press (OUP). doi:10.1093/jnci/djm231.
- Joshua, A M, V E Zannella, M R Downes, B Bowes, K Hersey, M Koritzinsky, M Schwab, et al.. 2014. “A Pilot ‘window of Opportunity’ Neoadjuvant Study of Metformin in Localised Prostate Cancer”. Prostate Cancer and Prostatic Diseases. Springer Science and Business Media LLC. doi:10.1038/pcan.2014.20.
- Sherifali, Diana, Kara Nerenberg, Eleanor Pullenayegum, Ji Emmy Cheng, and Hertzel C. Gerstein. 2010. “The Effect of Oral Antidiabetic Agents on A1C Levels”. Diabetes Care. American Diabetes Association. doi:10.2337/dc09-1727.
- Bailey, Clifford J., and Robert C. Turner. 1996. “Metformin”. Edited by Alastair J.J. Wood. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejm199602293340906.
- Nathan, David M. 1998. “Some Answers, More Controversy, from UKPDS”. The Lancet. Elsevier BV. doi:10.1016/s0140-6736(98)22937-0.
- Hong, Jie, Yifei Zhang, Shenghan Lai, Ankang Lv, Qing Su, Yan Dong, Zhiguang Zhou, et al.. 2013. “Effects of Metformin Versus Glipizide on Cardiovascular Outcomes in Patients with Type 2 Diabetes and Coronary Artery Disease”. Diabetes Care. American Diabetes Association. doi:10.2337/dc12-0719.
- “United Kingdom Prospective Diabetes Study 24: A 6-year, Randomized, Controlled Trial Comparing Sulfonylurea, Insulin, and Metformin Therapy in Patients with Newly Diagnosed Type 2 Diabetes That Could Not Be Controlled with Diet Therapy”. 1998. “United Kingdom Prospective Diabetes Study 24: A 6-year, Randomized, Controlled Trial Comparing Sulfonylurea, Insulin, and Metformin Therapy in Patients with Newly Diagnosed Type 2 Diabetes That Could Not Be Controlled with Diet Therapy”. Annals of Internal Medicine. American College of Physicians. doi:10.7326/0003-4819-128-3-199802010-00001.
- Margetts, B. M. 1995. “United Kingdom Prospective Diabetes Study”. Bmj. BMJ. doi:10.1136/bmj.310.6985.1005c.
- Hermann, Leif S, Bengt Scherstén, Per-Olof Bitzén, Thomas Kjellström, Folke Lindgärde, and Arne Melander. 1994. “Therapeutic Comparison of Metformin and Sulfonylurea, Alone and in Various Combinations: A Double-blind Controlled Study”. Diabetes Care. American Diabetes Association. doi:10.2337/diacare.17.10.1100.
- Orchard, Trevor J., Marinella Temprosa, Ronald Goldberg, Steven Haffner, Robert Ratner, Santica Marcovina, Sarah Fowler, and for the Diabetes Prevention Program Research Group. 2005. “The Effect of Metformin and Intensive Lifestyle Intervention on the Metabolic Syndrome: The Diabetes Prevention Program Randomized Trial”. Annals of Internal Medicine. American College of Physicians. doi:10.7326/0003-4819-142-8-200504190-00009.
- Smith, Matthew R., Hang Lee, and David M. Nathan. 2006. “Insulin Sensitivity During Combined Androgen Blockade for Prostate Cancer”. The Journal of Clinical Endocrinology & Metabolism. The Endocrine Society. doi:10.1210/jc.2005-2507.
- Ma, Jing, Haojie Li, Ed Giovannucci, Lorelei Mucci, Weiliang Qiu, Paul L Nguyen, J Michael Gaziano, Michael Pollak, and Meir J Stampfer. 2008. “Prediagnostic Body-mass Index, Plasma C-peptide Concentration, and Prostate Cancer-specific Mortality in Men with Prostate Cancer: A Long-term Survival Analysis”. The Lancet Oncology. Elsevier BV. doi:10.1016/s1470-2045(08)70235-3.
- Spratt, Daniel E., Chi Zhang, Zachary S. Zumsteg, Xin Pei, Zhigang Zhang, and Michael J. Zelefsky. 2013. “Metformin and Prostate Cancer: Reduced Development of Castration-resistant Disease and Prostate Cancer Mortality”. European Urology. Elsevier BV. doi:10.1016/j.eururo.2012.12.004.
- Margel, David, David R. Urbach, Lorraine L. Lipscombe, Chaim M. Bell, Girish Kulkarni, Peter C. Austin, and Neil Fleshner. 2013. “Metformin Use and All-cause and Prostate Cancer–specific Mortality Among Men with Diabetes”. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). doi:10.1200/jco.2012.46.7043.
- Rothermundt, Christian, Stefanie Hayoz, Arnoud J. Templeton, Ralph Winterhalder, Räto T. Strebel, Daniela Bärtschi, Michael Pollak, et al.. 2014. “Metformin in Chemotherapy-naive Castration-resistant Prostate Cancer: A Multicenter Phase 2 Trial (SAKK 08/09)”. European Urology. Elsevier BV. doi:10.1016/j.eururo.2013.12.057.
- Johnson NP. Metformin use in women with polycystic ovary syndrome. Ann Transl Med. 2014 Jun;2(6):56. doi: 10.3978/j.issn.2305-5839.2014.04.15. Review.
- Generali, Joyce A., and Dennis J. Cada. 2013. “Metformin: Prevention and Treatment of Antipsychotic-induced Weight Gain”. Hospital Pharmacy. SAGE Publications. doi:10.1310/hpj4809-734.
- Saylor, Philip J., and Matthew R. Smith. 2013. “Metabolic Complications of Androgen Deprivation Therapy for Prostate Cancer”. Journal of Urology. Ovid Technologies (Wolters Kluwer Health). doi:10.1016/j.juro.2012.11.017.
- Forslund, Kristoffer, MetaHIT consortium, Falk Hildebrand, Trine Nielsen, Gwen Falony, Emmanuelle Le Chatelier, Shinichi Sunagawa, et al.. 2015. “Disentangling Type 2 Diabetes and Metformin Treatment Signatures in the Human Gut Microbiota”. Nature. Springer Science and Business Media LLC. doi:10.1038/nature15766.
- Feig, Denice S., and Robert G. Moses. 2011. “Metformin Therapy During Pregnancy”. Diabetes Care. American Diabetes Association. doi:10.2337/dc11-1153.
- Brackett, Carolyn C.. 2010. “Clarifying Metformin's Role and Risks in Liver Dysfunction”. Journal of the American Pharmacists Association. Elsevier BV. doi:10.1331/japha.2010.08090.
- Nguyen, Paul L., Shabbir M.H. Alibhai, Shehzad Basaria, Anthony V. D’Amico, Philip W. Kantoff, Nancy L. Keating, David F. Penson, Derek J. Rosario, Bertrand Tombal, and Matthew R. Smith. 2015. “Adverse Effects of Androgen Deprivation Therapy and Strategies to Mitigate Them”. European Urology. Elsevier BV. doi:10.1016/j.eururo.2014.07.010.
- Mohler, James L., Andrew J. Armstrong, Robert R. Bahnson, Anthony Victor D'Amico, Brian J. Davis, James A. Eastham, Charles A. Enke, et al.. 2016. “Prostate Cancer, Version 1.2016”. Journal of the National Comprehensive Cancer Network. Harborside Press, LLC. doi:10.6004/jnccn.2016.0004.
- Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 2001. “Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (adult Treatment Panel III)”. JAMA: The Journal of the American Medical Association. American Medical Association (AMA). doi:10.1001/jama.285.19.2486.
- Foretz, Marc, Bruno Guigas, Luc Bertrand, Michael Pollak, and Benoit Viollet. 2014. “Metformin: From Mechanisms of Action to Therapies”. Cell Metabolism. Elsevier BV. doi:10.1016/j.cmet.2014.09.018.
- Bridges, Hannah R., Andrew J. Y. Jones, Michael N. Pollak, and Judy Hirst. 2014. “Effects of Metformin and Other Biguanides on Oxidative Phosphorylation in Mitochondria”. Biochemical Journal. Portland Press Ltd.. doi:10.1042/bj20140620.
- Nobes, Jenny P., Stephen E.M. Langley, Tanya Klopper, David Russell-Jones, and Robert W. Laing. 2011. “A Prospective, Randomized Pilot Study Evaluating the Effects of Metformin and Lifestyle Intervention on Patients with Prostate Cancer Receiving Androgen Deprivation Therapy”. BJU International. Wiley. doi:10.1111/j.1464-410x.2011.10555.x.
- Goldenberg, Ronald, and Zubin Punthakee. 2013. “Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome”. Canadian Journal of Diabetes. Elsevier BV. doi:10.1016/j.jcjd.2013.01.011.
- Aaronson, N. K., S. Ahmedzai, B. Bergman, M. Bullinger, A. Cull, N. J. Duez, A. Filiberti, et al.. 1993. “The European Organization for Research and Treatment of Cancer QLQ-C30: A Quality-of-life Instrument for Use in International Clinical Trials in Oncology”. JNCI Journal of the National Cancer Institute. Oxford University Press (OUP). doi:10.1093/jnci/85.5.365.
- Segal, Roanne J., Robert D. Reid, Kerry S. Courneya, Ronald J. Sigal, Glen P. Kenny, Denis G. Prud'Homme, Shawn C. Malone, George A. Wells, Chris G. Scott, and Monika E. Slovinec D'Angelo. 2009. “Randomized Controlled Trial of Resistance or Aerobic Exercise in Men Receiving Radiation Therapy for Prostate Cancer”. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). doi:10.1200/jco.2007.15.4963.
- Kurtze, Nanna, Vegar Rangul, Bo-Egil Hustvedt, and W Dana Flanders. 2008. “Reliability and Validity of Self-reported Physical Activity in the Nord-trøndelag Health Study — HUNT 1”. Scandinavian Journal of Public Health. SAGE Publications. doi:10.1177/1403494807085373.
- Rosenberg, Dori E., Gregory J. Norman, Nicole Wagner, Kevin Patrick, Karen J. Calfas, and James F. Sallis. 2010. “Reliability and Validity of the Sedentary Behavior Questionnaire (SBQ) for Adults”. Journal of Physical Activity and Health. Human Kinetics. doi:10.1123/jpah.7.6.697.
- Antuna-Puente, B., E. Disse, R. Rabasa-Lhoret, M. Laville, J. Capeau, and J.-P. Bastard. 2011. “How Can We Measure Insulin Sensitivity/resistance?”. Diabetes & Metabolism. Elsevier BV. doi:10.1016/j.diabet.2011.01.002.
- Borai, Anwar, Callum Livingstone, Ibrahim Kaddam, and Gordon Ferns. 2011. “Selection of the Appropriate Method for the Assessment of Insulin Resistance”. BMC Medical Research Methodology. Springer Science and Business Media LLC. doi:10.1186/1471-2288-11-158.
- Katz, Arie, Sridhar S. Nambi, Kieren Mather, Alain D. Baron, Dean A. Follmann, Gail Sullivan, and Michael J. Quon. 2000. “Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity in Humans”. The Journal of Clinical Endocrinology & Metabolism. The Endocrine Society. doi:10.1210/jcem.85.7.6661.
- Riediger, Natalie D., and Ian Clara. 2011. “Prevalence of Metabolic Syndrome in the Canadian Adult Population”. Canadian Medical Association Journal. CMA Joule Inc.. doi:10.1503/cmaj.110070.
- Osoba, D, G Rodrigues, J Myles, B Zee, and J Pater. 1998. “Interpreting the Significance of Changes in Health-related Quality-of-life Scores.”. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). doi:10.1200/jco.1998.16.1.139.
- Roy, S., S. Malone, S. Grimes, and S.C. Morgan. 2021. “Impact of Concomitant Medications on Biochemical Outcome in Localised Prostate Cancer Treated with Radiotherapy and Androgen Deprivation Therapy”. Clinical Oncology. Elsevier BV. doi:10.1016/j.clon.2020.09.005.
- Ford, Earl S., and Chaoyang Li. 2008. “Metabolic Syndrome and Health-related Quality of Life Among U.S. Adults”. Annals of Epidemiology. Elsevier BV. doi:10.1016/j.annepidem.2007.10.009.
- Kaplan, Norman M.. 1996. “The Deadly Quartet and the Insulin Resistance Syndrome: An Historical Overview”. Hypertension Research. Japanese Society of Hypertension. doi:10.1291/hypres.19.supplementi_s9.
- Mottillo, Salvatore, Kristian B. Filion, Jacques Genest, Lawrence Joseph, Louise Pilote, Paul Poirier, Stéphane Rinfret, Ernesto L. Schiffrin, and Mark J. Eisenberg. 2010. “The Metabolic Syndrome and Cardiovascular Risk”. Journal of the American College of Cardiology. Elsevier BV. doi:10.1016/j.jacc.2010.05.034.
- Lipska, Kasia J., Clifford J. Bailey, and Silvio E. Inzucchi. 2011. “Use of Metformin in the Setting of Mild-to-moderate Renal Insufficiency”. Diabetes Care. American Diabetes Association. doi:10.2337/dc10-2361.
- Inzucchi, Silvio E., Kasia J. Lipska, Helen Mayo, Clifford J. Bailey, and Darren K. McGuire. 2014. “Metformin in Patients with Type 2 Diabetes and Kidney Disease”. Jama. American Medical Association (AMA). doi:10.1001/jama.2014.15298.
- Alberti, K.G.M.M., Robert H. Eckel, Scott M. Grundy, Paul Z. Zimmet, James I. Cleeman, Karen A. Donato, Jean-Charles Fruchart, W. Philip T. James, Catherine M. Loria, and Sidney C. Smith Jr. 2009. “Harmonizing the Metabolic Syndrome”. Circulation. Ovid Technologies (Wolters Kluwer Health). doi:10.1161/circulationaha.109.192644.
- Canadian Cancer Society. Canadian Cancer Statistics 2015: Canadian Cancer Society; 2015 [Available from: http://www.cancer.ca/].
- Rothermundt, Christian, Stefanie Hayoz, Arnoud J. Templeton, Ralph Winterhalder, Räto T. Strebel, Daniela Bärtschi, Michael Pollak, et al.. 2014. “Metformin in Chemotherapy-naive Castration-resistant Prostate Cancer: A Multicenter Phase 2 Trial (SAKK 08/09)”. European Urology. Elsevier BV. doi:10.1016/j.eururo.2013.12.057.
- Alberti, K.G.M.M., Robert H. Eckel, Scott M. Grundy, Paul Z. Zimmet, James I. Cleeman, Karen A. Donato, Jean-Charles Fruchart, W. Philip T. James, Catherine M. Loria, and Sidney C. Smith Jr. 2009. “Harmonizing the Metabolic Syndrome”. Circulation. Ovid Technologies (Wolters Kluwer Health). doi:10.1161/circulationaha.109.192644.
- Kylin E. Studien ueber das Hypertonie-Hyperglykaemie-Hyperurikaemiesydrom. Zentralblatt fuer Innere Medizin. 1923;44:105-27.
- Crook, Juanita M., Christopher J. O'Callaghan, Graeme Duncan, David P. Dearnaley, Celestia S. Higano, Eric M. Horwitz, Eliot Frymire, et al.. 2012. “Intermittent Androgen Suppression for Rising PSA Level After Radiotherapy”. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejmoa1201546.
- Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65. Erratum In: Lancet 1998 Nov 7;352(9139):1558.
- Brackett CC. Clarifying metformin's role and risks in liver dysfunction. J Am Pharm Assoc (2003). 2010 May-Jun;50(3):407-10. doi: 10.1331/JAPhA.2010.08090.
- Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. 2011 Jun;34(6):1431-7. doi: 10.2337/dc10-2361. No abstract available.
- Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes. 1992 Jun;41(6):715-22. doi: 10.2337/diab.41.6.715.
- Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996 Feb 29;334(9):574-9. doi: 10.1056/NEJM199602293340906. No abstract available.
- Nguyen PL, Alibhai SM, Basaria S, D'Amico AV, Kantoff PW, Keating NL, Penson DF, Rosario DJ, Tombal B, Smith MR. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015 May;67(5):825-36. doi: 10.1016/j.eururo.2014.07.010. Epub 2014 Aug 2.
- Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, Rinfret S, Schiffrin EL, Eisenberg MJ. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010 Sep 28;56(14):1113-32. doi: 10.1016/j.jacc.2010.05.034.
- Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, Frymire E, Malone S, Chin J, Nabid A, Warde P, Corbett T, Angyalfi S, Goldenberg SL, Gospodarowicz MK, Saad F, Logue JP, Hall E, Schellhammer PF, Ding K, Klotz L. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012 Sep 6;367(10):895-903. doi: 10.1056/NEJMoa1201546. Erratum In: N Engl J Med. 2012 Dec 6;367(23):2262.
- Rosenberg DE, Norman GJ, Wagner N, Patrick K, Calfas KJ, Sallis JF. Reliability and validity of the Sedentary Behavior Questionnaire (SBQ) for adults. J Phys Act Health. 2010 Nov;7(6):697-705. doi: 10.1123/jpah.7.6.697.
- Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595-607. doi: 10.2337/diab.37.12.1595.
- Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Pedersen HK, Arumugam M, Kristiansen K, Voigt AY, Vestergaard H, Hercog R, Costea PI, Kultima JR, Li J, Jorgensen T, Levenez F, Dore J; MetaHIT consortium, Nielsen HB, Brunak S, Raes J, Hansen T, Wang J, Ehrlich SD, Bork P, Pedersen O. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015 Dec 10;528(7581):262-266. doi: 10.1038/nature15766. Epub 2015 Dec 2. Erratum In: Nature. 2017 May 3;545(7652):116.
- Tsai HK, D'Amico AV, Sadetsky N, Chen MH, Carroll PR. Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J Natl Cancer Inst. 2007 Oct 17;99(20):1516-24. doi: 10.1093/jnci/djm168. Epub 2007 Oct 9.
- Segal RJ, Reid RD, Courneya KS, Malone SC, Parliament MB, Scott CG, Venner PM, Quinney HA, Jones LW, D'Angelo ME, Wells GA. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol. 2003 May 1;21(9):1653-9. doi: 10.1200/JCO.2003.09.534.
- Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998 Jan;16(1):139-44. doi: 10.1200/JCO.1998.16.1.139.
- Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000 Jul;85(7):2402-10. doi: 10.1210/jcem.85.7.6661.
- Pollak MN. Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov. 2012 Sep;2(9):778-90. doi: 10.1158/2159-8290.CD-12-0263. Epub 2012 Aug 27.
- Malik S, Wong ND, Franklin SS, Kamath TV, L'Italien GJ, Pio JR, Williams GR. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation. 2004 Sep 7;110(10):1245-50. doi: 10.1161/01.CIR.0000140677.20606.0E. Epub 2004 Aug 23.
- Pollak M. Overcoming Drug Development Bottlenecks With Repurposing: Repurposing biguanides to target energy metabolism for cancer treatment. Nat Med. 2014 Jun;20(6):591-3. doi: 10.1038/nm.3596. No abstract available.
- Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002 Dec 4;288(21):2709-16. doi: 10.1001/jama.288.21.2709.
- Miettola J, Niskanen LK, Viinamaki H, Sintonen H, Kumpusalo E. Metabolic syndrome is associated with impaired health-related quality of life: Lapinlahti 2005 study. Qual Life Res. 2008 Oct;17(8):1055-62. doi: 10.1007/s11136-008-9386-6. Epub 2008 Aug 31.
- Mohler JL, Armstrong AJ, Bahnson RR, D'Amico AV, Davis BJ, Eastham JA, Enke CA, Farrington TA, Higano CS, Horwitz EM, Hurwitz M, Kane CJ, Kawachi MH, Kuettel M, Lee RJ, Meeks JJ, Penson DF, Plimack ER, Pow-Sang JM, Raben D, Richey S, Roach M 3rd, Rosenfeld S, Schaeffer E, Skolarus TA, Small EJ, Sonpavde G, Srinivas S, Strope SA, Tward J, Shead DA, Freedman-Cass DA. Prostate Cancer, Version 1.2016. J Natl Compr Canc Netw. 2016 Jan;14(1):19-30. doi: 10.6004/jnccn.2016.0004.
- Kaplan NM. The deadly quartet and the insulin resistance syndrome: an historical overview. Hypertens Res. 1996 Jun;19 Suppl 1:S9-11. doi: 10.1291/hypres.19.supplementi_s9.
- Carmack Taylor CL, Demoor C, Smith MA, Dunn AL, Basen-Engquist K, Nielsen I, Pettaway C, Sellin R, Massey P, Gritz ER. Active for Life After Cancer: a randomized trial examining a lifestyle physical activity program for prostate cancer patients. Psychooncology. 2006 Oct;15(10):847-62. doi: 10.1002/pon.1023.
- Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B. Metformin: from mechanisms of action to therapies. Cell Metab. 2014 Dec 2;20(6):953-66. doi: 10.1016/j.cmet.2014.09.018. Epub 2014 Oct 30.
- Pollak M. Potential applications for biguanides in oncology. J Clin Invest. 2013 Sep;123(9):3693-700. doi: 10.1172/JCI67232. Epub 2013 Sep 3.
- Venkateswaran V, Haddad AQ, Fleshner NE, Fan R, Sugar LM, Nam R, Klotz LH, Pollak M. Association of diet-induced hyperinsulinemia with accelerated growth of prostate cancer (LNCaP) xenografts. J Natl Cancer Inst. 2007 Dec 5;99(23):1793-800. doi: 10.1093/jnci/djm231. Epub 2007 Nov 27.
- Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, Fowler S; Diabetes Prevention Program Research Group. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med. 2005 Apr 19;142(8):611-9. doi: 10.7326/0003-4819-142-8-200504190-00009.
- Rothermundt C, Hayoz S, Templeton AJ, Winterhalder R, Strebel RT, Bartschi D, Pollak M, Lui L, Endt K, Schiess R, Ruschoff JH, Cathomas R, Gillessen S. Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09). Eur Urol. 2014 Sep;66(3):468-74. doi: 10.1016/j.eururo.2013.12.057. Epub 2014 Jan 4.
- Feig DS, Moses RG. Metformin therapy during pregnancy: good for the goose and good for the gosling too? Diabetes Care. 2011 Oct;34(10):2329-30. doi: 10.2337/dc11-1153. No abstract available.
- Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Goldenberg R, Punthakee Z. Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome. Can J Diabetes. 2013 Apr;37 Suppl 1:S8-11. doi: 10.1016/j.jcjd.2013.01.011. Epub 2013 Mar 26. No abstract available.
- Antuna-Puente B, Disse E, Rabasa-Lhoret R, Laville M, Capeau J, Bastard JP. How can we measure insulin sensitivity/resistance? Diabetes Metab. 2011 Jun;37(3):179-88. doi: 10.1016/j.diabet.2011.01.002. Epub 2011 Mar 23.
- Borai A, Livingstone C, Kaddam I, Ferns G. Selection of the appropriate method for the assessment of insulin resistance. BMC Med Res Methodol. 2011 Nov 23;11:158. doi: 10.1186/1471-2288-11-158.
- Basaria S, Muller DC, Carducci MA, Egan J, Dobs AS. Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy. Cancer. 2006 Feb 1;106(3):581-8. doi: 10.1002/cncr.21642.
- United Kingdom Prospective Diabetes Study 24: a 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. United Kingdom Prospective Diabetes Study Group. Ann Intern Med. 1998 Feb 1;128(3):165-75. doi: 10.7326/0003-4819-128-3-199802010-00001.
- Saylor PJ, Smith MR. Metabolic complications of androgen deprivation therapy for prostate cancer. J Urol. 2013 Jan;189(1 Suppl):S34-42; discussion S43-4. doi: 10.1016/j.juro.2012.11.017.
- Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA. 2014 Dec 24-31;312(24):2668-75. doi: 10.1001/jama.2014.15298.
- Solymoss BC, Bourassa MG, Campeau L, Sniderman A, Marcil M, Lesperance J, Levesque S, Varga S. Effect of increasing metabolic syndrome score on atherosclerotic risk profile and coronary artery disease angiographic severity. Am J Cardiol. 2004 Jan 15;93(2):159-64. doi: 10.1016/j.amjcard.2003.09.032.
- Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 May 16;285(19):2486-97. doi: 10.1001/jama.285.19.2486. No abstract available.
- Braga-Basaria M, Dobs AS, Muller DC, Carducci MA, John M, Egan J, Basaria S. Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy. J Clin Oncol. 2006 Aug 20;24(24):3979-83. doi: 10.1200/JCO.2006.05.9741.
- Sherifali D, Nerenberg K, Pullenayegum E, Cheng JE, Gerstein HC. The effect of oral antidiabetic agents on A1C levels: a systematic review and meta-analysis. Diabetes Care. 2010 Aug;33(8):1859-64. doi: 10.2337/dc09-1727. Epub 2010 May 18.
- Hermann LS, Schersten B, Bitzen PO, Kjellstrom T, Lindgarde F, Melander A. Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study. Diabetes Care. 1994 Oct;17(10):1100-9. doi: 10.2337/diacare.17.10.1100.
- Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab. 2006 Apr;91(4):1305-8. doi: 10.1210/jc.2005-2507. Epub 2006 Jan 24.
- Johnson NP. Metformin use in women with polycystic ovary syndrome. Ann Transl Med. 2014 Jun;2(6):56. doi: 10.3978/j.issn.2305-5839.2014.04.15.
- Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365.
- Riediger ND, Clara I. Prevalence of metabolic syndrome in the Canadian adult population. CMAJ. 2011 Oct 18;183(15):E1127-34. doi: 10.1503/cmaj.110070. Epub 2011 Sep 12. Erratum In: CMAJ. 2019 Feb 4;191(5):E141.
- Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Pedersen HK, Arumugam M, Kristiansen K, Voigt AY, Vestergaard H, Hercog R, Costea PI, Kultima JR, Li J, Jorgensen T, Levenez F, Dore J; MetaHIT consortium; Nielsen HB, Brunak S, Raes J, Hansen T, Wang J, Ehrlich SD, Bork P, Pedersen O. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015 Dec 10;528(7581):262-266. doi: 10.1038/nature15766. Epub 2015 Dec 2. Erratum In: Nature. 2017 May 3;545(7652):116.
- Canadian Diabetes Association Clinical Practice Guidelines Expert Committee; Goldenberg R, Punthakee Z. Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome. Can J Diabetes. 2013 Apr;37 Suppl 1:S8-11. doi: 10.1016/j.jcjd.2013.01.011. Epub 2013 Mar 26. No abstract available.
- 2018. "Metformin in Patients Initiating ADT as Prevention and Intervention of Metabolic Syndrome". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03031821.
Frequently Asked Questions
For what purpose is Metformin most commonly prescribed?
"Metformin is a medication that is regularly prescribed to patients with type 1 diabetes mellitus, polycystic ovary syndrome, and diabetic ketoacidosis." - Anonymous Online Contributor
What similar research has been conducted using Metformin?
"Metformin was first studied in clinical trials by George Washington University in 2002. To date, 1260 have completed similar experiments. Right now, there are 180 active studies involving metformin with a high concentration of these being located in Toronto, Canada." - Anonymous Online Contributor
Are there any vacancies in this study for new participants?
"Yes, the clinicaltrials.gov website contains information suggesting that this trial is still actively recruiting patients. This particular study was first posted on July 12th, 2018 and was last updated on July 11th, 2022. They are looking for a total of 300 participants spread out across 15 different locations." - Anonymous Online Contributor
Are there any sites outside of Canada conducting this research?
"This research is being conducted at 15 different hospitals, including the Princess Margaret Cancer Centre (Princess Margaret Hospital) in Toronto, the Centre Hospitalier de L'Universite de Montreal (CHUM) in Montreal, and Northeast Cancer Centre in Sudbury." - Anonymous Online Contributor
What is the Metformin drug's official government rating?
"There is prior clinical data supporting Metformin's safety, so it received a score of 3." - Anonymous Online Contributor
Could you give an estimate of how many people are involved in this clinical trial?
"To run this clinical study, we require 300 individuals who meet the pre-specified inclusion criteria. These participants can come from various locations such as Princess Margaret Cancer Centre (Princess Margaret Hospital) in Toronto, Ontario and Centre Hospitalier de L'Universite de Montreal (CHUM) in Montreal, Quebec." - Anonymous Online Contributor