Assessing Bladder Cancer Risk in Type 2 Diabetes Clinical Trials: the Dapagliflozin Drug Development Program as a 'Case Study'

Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders
Agata PtaszynskaKristina M Johnsson

Abstract

Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, decreases plasma glucose levels by suppressing renal glucose reabsorption and increasing urinary glucose excretion. Previously published pre-clinical data suggest that dapagliflozin lacks carcinogenic potential. This article reviews data on bladder cancer with dapagliflozin to illustrate the challenges in assessing bladder cancer in drug development programs in patients with type 2 diabetes mellitus (T2DM). Clinical cases of bladder cancer were analyzed in a pooled population of >9000 patients in 21 phase 2b/3 dapagliflozin clinical trials of up to 208 weeks' duration. In the 21-study pool, demographic and baseline characteristics were generally consistent between dapagliflozin and comparator groups. The overall incidence of malignancies was also balanced between the treatment groups, with an incidence rate ratio (IRR) of 1.035 [95% confidence interval (CI): 0.724, 1.481]. Nine of 5936 dapagliflozin-treated patients and 1 of 3403 comparator-treated patients reported bladder cancer, with an IRR of 5.168 (95% CI: 0.677, 233.55). All of these patients had clinical attributes typical of bladder cancer in the general population (≥60-year-old males; 8 of the 10 patients were...Continue Reading

References

Jan 1, 1970·Advances in Cancer Research·D B Clayson, E H Cooper
Jan 1, 1981·Epidemiologic Reviews·G M Matanoski, E A Elliott
Apr 5, 1995·Journal of the National Cancer Institute·L B TravisJ Adami
Jan 1, 1993·Epidemiologic Reviews·K E Malone
Mar 1, 1996·Annals of Internal Medicine·C Talar-WilliamsM C Sneller
Aug 7, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Crystal R WaitesBeth E Schilling
Jul 16, 2008·Urology·Emilie K JohnsonCheryl T Lee
Nov 11, 2008·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Muhammad A Abdul-Ghani, Ralph A DeFronzo
Dec 31, 2008·Diabetes Care·James F ListFred T Fiedorek
Apr 3, 2009·BJU International·Paul CrowFrancis Keeley
Nov 18, 2009·Journal of the National Cancer Institute·Dalsu BarisDebra T Silverman
Jul 1, 2010·Diabetes Care·Edward GiovannucciDouglas Yee
Mar 21, 2012·Annals of Internal Medicine·John P H WildingUNKNOWN Dapagliflozin 006 Study Group
Apr 25, 2012·Current Diabetes Reports·Muhammad A Abdul-GhaniRalph A DeFronzo
May 12, 2012·British Journal of Clinical Pharmacology·Li WeiIsla S Mackenzie
Sep 6, 2012·The British Journal of General Practice : the Journal of the Royal College of General Practitioners·Elizabeth A ShephardWilliam T Hamilton
Sep 27, 2012·Diabetes Research and Clinical Practice·Carlos AlvesAna F Macedo
Oct 2, 2012·International Journal of Cancer. Journal International Du Cancer·Christina C NewtonEric J Jacobs
Nov 22, 2012·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Chin-Hsiao Tseng, Farn-Hsuan Tseng
Feb 12, 2013·Current Diabetes Reports·Markolf Hanefeld, Peter Bramlage
Nov 5, 2013·Diabetes Technology & Therapeutics·Hong FangYanping Zhao
Jan 30, 2014·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Timothy P ReillyMark Tirmenstein
Feb 4, 2014·Diabetes Research and Clinical Practice·Matteo MonamiEdoardo Mannucci
Feb 4, 2014·The American Journal of Medicine·David F FriedlanderDaniel A Barocas
Feb 26, 2014·The American Journal of Medicine·Atul B ShinagareRamin Khorasani
Jun 20, 2014·Indian Journal of Endocrinology and Metabolism·V BalajiM Janarthinakani
Oct 8, 2014·Chemico-biological Interactions·Sandra De JongheMark D Johnson
Nov 28, 2014·British Journal of Cancer·S H VermeulenL A Kiemeney

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Citations

Aug 20, 2016·Current Diabetes Reports·André J Scheen
Nov 8, 2016·Expert Opinion on Drug Metabolism & Toxicology·Vasilios TsimihodimosMoses S Elisaf
Feb 17, 2017·Therapeutic Advances in Endocrinology and Metabolism·Vasileios AndrianesisJohn Doupis
Oct 7, 2017·Expert Review of Clinical Pharmacology·André J Scheen
Oct 19, 2017·Postgraduate Medicine·Sebastian Filippas-NtekouanMoses S Elisaf
Sep 15, 2017·Diabetologia·Altamash M Y Shaikh
Apr 27, 2019·Expert Opinion on Therapeutic Patents·Jyotsana Pandey, Akhilesh K Tamrakar
Jun 1, 2019·Expert Opinion on Drug Safety·Elizabeth Mary LamosStephen N Davis
Jul 28, 2017·Expert Opinion on Drug Safety·Marco TuccoriCorrado Blandizzi
Nov 14, 2019·Endocrine Reviews·Iliana C Lega, Lorraine L Lipscombe
Jan 10, 2020·Future Cardiology·Dalal Y Al-Bazz, John Ph Wilding
Jun 6, 2020·Cells·Swayam Prakash Srivastava, Julie E Goodwin
Mar 15, 2018·Pathology Oncology Research : POR·Jeny LaskarYashmin Choudhury
Jul 25, 2018·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·John WildingAdie Viljoen
Apr 2, 2019·Expert Opinion on Drug Safety·André J Scheen
Jun 27, 2019·Drugs·Sohita Dhillon
Dec 13, 2016·Nature Reviews. Nephrology·Ralph A DeFronzoMuhammad Abdul-Ghani
Aug 29, 2019·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Dhiren K Patel, Jodi Strong
Jan 7, 2020·Diabetes & Metabolism Journal·Sunghwan Suh, Kwang Won Kim
Aug 23, 2020·Journal of Clinical Pharmacology·Montserrat GarcíaCarmelo Aguirre
Dec 3, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gadi ShlomaiEmily Jane Gallagher

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Methods Mentioned

BETA
xenograft

Clinical Trials Mentioned

NCT00069784
NCT00972244
NCT01031680
NCT00683878
NCT00673231
NCT00528879
NCT00660907
NCT01042977

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