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Pioglitazone (Actos, Glustin)

A Drug That Transformed Diabetes Therapy

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Drug Discovery in Japan
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Abstract

Pioglitazone was an early member of a new category of diabetes treatment drugs called insulin sensitizers, pioneered by Takeda Pharmaceutical. It is used for the treatment of Type 2 diabetes, and acts by lowering blood glucose levels. The thiazolidinedione backbone discovered by Takeda Pharmaceutical was widely adopted in industry. Research on pioglitazone began as a result of serendipitous discovery of its lead compound during research on lipid-lowering agents. New animal models made a major contribution to understanding the pathogenesis of diabetes in basic research, but also led the researchers to the discovery of compounds with thiazolidinedione backbone that improve insulin sensitivity. Although ciglitazone, the first compound studied in clinical trials, failed, pioglitazone was discovered and selected as a candidate compound based on its potent activity, and low propensity to induce side effects. Pioglitazone is a breakthrough drug generated by the culmination of basic research, including the development of animal models, careful screening techniques, and excellent synthesis technologies.

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Notes

  1. 1.

    Novo Nordisk Pharma Limited. Advances in Insulin Preparations 2: Looking for Human Insulin. http://www.novonordisk.co.jp/documents/article_page/document/CO_tcinsulin_011.asp (accessed 7 August 2014).

References

  • Astellas Pharma Inc. (2005). Summary of fiscal 2005 interim summary. http://www.astellas.com/jp/ir/library/pdf/h_pre2006_jp.pdf. Accessed in July 3, 2014.

  • El-Hage, J. (2006). Peroxisome Proliferator-Activated Receptor (PPAR) agonists preclinical and clinical cardiac safety considerations. http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ucm119071.pdf. Accessed in May 16, 2014.

  • Himsworth, H. P. (1936). Diabetes mellitus: Its differentiation into insulin-sensitive and insulin-insensitive types. The Lancet, 227(5864), 127–130.

    Article  Google Scholar 

  • Ikeda, H. (1998). Introduction to the study of diabetes mellitus by Takeda. The Japanese Society of Diabetes and Obese Zoology News Letter 2(2). http://jsedo.jp/news/nl2-2.html. Accessed in May 16, 2014.

  • Ikeda, H., & Sugiyama, Y. (2001). Insulin-resistance improving effects of pioglitazone. Journal of Science, Japan drug, 117(5), 335–342.

    Google Scholar 

  • Kawai, K. (2007). Insulin-sensitizing drugs and “frosted” carcasses. http://www.somos.co.jp/solution/d/076.html (accessed in May 16, 2014).

  • Kawamatsu, Y., & Fujita, T. (1981). Useful as remedies for diabetes and hyperlipemia, US4287200A.

    Google Scholar 

  • Kyorin Pharmaceutical Co., Ltd. (2003). Discontinuation of development of KRP-297, a diabetes treatment at Merck, U.S.A. (Phase 3 clinical trial).

    Google Scholar 

  • Lehmann, J. M., Moore, L. B., Smith-Oliver, T. A., Wilkison, W. O., Willson, T. M., & Kliewer, S. A. (1995). An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). Journal of Biological Chemistry, 270(22), 12953–12956.

    Article  Google Scholar 

  • Makino, H. (2006). Diabetes mellitus and Kappadkia. News Letter of the Japanese Society for Diabetes and Obesity, Zoological Society 10(2). http://jsedo.jp/news/nl10-2.html. Accessed in February 28, 2014.

  • Maruyama, K. (1992). The New Insulin Story. Tokyo Dojin.

    Google Scholar 

  • Meguro, K. (1991). Seeking new treatments for diabetes. Pharmacia, 27(9), 899–902.

    Google Scholar 

  • Meguro, K. (2014). Luck, stolidity, and perseverance in drug discovery. In Kinki Division of Chemistry Lecture Meeting, June 19, 2014. http://pe-eco.jp/articles/show/378. Accessed in August 7, 2014.

  • National Diabetes Data Group. (1979). Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes, 28(12), 1039–1057.

    Article  Google Scholar 

  • Nikkei Bio-Business. (2003, March). Competition for insulin resistance improvement drug (pp. 131–133).

    Google Scholar 

  • Ninomiya, R. (1996). Insulin-finding banting for $1. Medicina, 33(3), 612–613.

    Google Scholar 

  • Obayashi, M. (2008). From our experience in new drug development in the United States-centering on the development of Actos. In The Japanese Society of Pharmacopoeia (Ed.), The Pharmaceutical Expert Workshop Series 9: How to Learn from Practical Cases-How to Develop New Drugs Overseas-To Find Topics of Actos Success (pp. 2–34).

    Google Scholar 

  • Ono Pharmaceutical Co., Ltd. (2003). ONO-5816, Diabetes Treatment. http://www.ono.co.jp/jpnw/news/pdf/2003/n03_0219.pdf. Accessed in July 3, 2014.

  • Sakai, S. (1998). Fighting diabetes from a history perspective. Diabetes, 41(2), 89–93.

    Google Scholar 

  • Seino, S., Nanjo, K., Tajima, N., Kadowaki, T., Kashiwagi, A., Araki, E., et al. (2010). The Committee Report on Classification and Diagnostic Criteria of Diabetes Mellitus 53(6), 450–467.

    Google Scholar 

  • Sohda, T., Kawamatsu, Y., Fujita, T., Meguro, K., & Ikeda, H. (2002). Creation of pioglitazone, an insulin-sensitizing drug. Yakugaku Zasshi, 122(11), 909–918.

    Article  Google Scholar 

  • Takeda Pharmaceutical Co. Ltd. (1999). Data on Actos (Pioglitazone hydrochloride). http://www.info.pmda.go.jp/shinyaku/g990913/01ctdp_1-354.pdf. Accessed in February 10, 2014.

  • Takeda Pharmaceutical Co. Ltd. (2008). Birth and Evidence of Japanese World Pharmaceuticals (23) Pioglitazone (Actos®). Medicine 62(11), 637–638.

    Google Scholar 

  • Tsutani, K. (2007). Drug withdrawal. Pharmacia, 43(1), 1097–1102.

    Google Scholar 

  • World Health Organization. (1980). WHO Expert Committee on Diabetes Mellitus [meeting held in Geneva from 25 September to 1 October 1979]: second report. http://whqlibdoc.who.int/trs/WHO_TRS_646.pdf. Accessed in May 16, 2014.

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Correspondence to Naoki Takada .

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Takada, N., Genda, K. (2019). Pioglitazone (Actos, Glustin). In: Nagaoka, S. (eds) Drug Discovery in Japan. Springer, Singapore. https://doi.org/10.1007/978-981-13-8906-1_10

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  • DOI: https://doi.org/10.1007/978-981-13-8906-1_10

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