The Potential of Dapagliflozin Plus Exenatide in Obese Insulin-resistant Patients

Summary

This is a 28-week, multi-center, randomized, double-blind, placebo-controlled trial to study a potential synergistic effect of Dapagliflozin plus Exenatide once-weekly in combination with high-dose intensive insulin therapy compared to Placebo in obese insulin-resistant patients with Type 2 Diabetes mellitus (T2DM) and inadequate glycemic control (HbA1c≥8.0% and ≤ 11.0%).

Timeline

Start

2018-02-19

Primary completion

2019-04-01

Completion

2019-08-05

Publications

• Background Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond. Drugs Context. 2015 Jul 9;4:212283. doi: 10.7573/dic.212283. eCollection 2015.
• Background Wilding JP, Woo V, Soler NG, Pahor A, Sugg J, Rohwedder K, Parikh S; Dapagliflozin 006 Study Group. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med. 2012 Mar 20;156(6):405-15. doi: 10.7326/0003-4819-156-6-201203200-00003.
• Background Finkelstein EA, Khavjou OA, Thompson H, Trogdon JG, Pan L, Sherry B, Dietz W. Obesity and severe obesity forecasts through 2030. Am J Prev Med. 2012 Jun;42(6):563-70. doi: 10.1016/j.amepre.2011.10.026.
• Background Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012 Jun;35(6):1364-79. doi: 10.2337/dc12-0413. Epub 2012 Apr 19. No abstract available.
• Background Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2012 Jun;55(6):1577-96. doi: 10.1007/s00125-012-2534-0. Epub 2012 Apr 20. No abstract available.
• Background Tatarkiewicz K, Polizzi C, Villescaz C, D'Souza LJ, Wang Y, Janssen S, Parkes DG. Combined antidiabetic benefits of exenatide and dapagliflozin in diabetic mice. Diabetes Obes Metab. 2014 Apr;16(4):376-80. doi: 10.1111/dom.12237. Epub 2013 Dec 9.
• Background Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: update regarding thiazolidinediones: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2008 Jan;31(1):173-5. doi: 10.2337/dc08-9016. No abstract available.
• Background Wangnoo SK, Sethi B, Sahay RK, John M, Ghosal S, Sharma SK. Treat-to-target trials in diabetes. Indian J Endocrinol Metab. 2014 Mar;18(2):166-74. doi: 10.4103/2230-8210.129106.
• Background Holman R. Metformin as first choice in oral diabetes treatment: the UKPDS experience. Journ Annu Diabetol Hotel Dieu. 2007:13-20.
• Background Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, Trautmann M, Porter L. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011 May;96(5):1301-10. doi: 10.1210/jc.2010-2081. Epub 2011 Feb 9.
• Background Diamant M, Van Gaal L, Stranks S, Northrup J, Cao D, Taylor K, Trautmann M. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010 Jun 26;375(9733):2234-43. doi: 10.1016/S0140-6736(10)60406-0.
• Background Sharma S, Jain S. Prevalence of Obesity among Type-2 Diabetics. J Hum Ecol 2009;25:31-5.
• Background Dixon JB, O'Brien PE. Health outcomes of severely obese type 2 diabetic subjects 1 year after laparoscopic adjustable gastric banding. Diabetes Care. 2002 Feb;25(2):358-63. doi: 10.2337/diacare.25.2.358.
• Background 2012. Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus n.d. ema.europa.eu.
• Background Anderson SL. Dapagliflozin efficacy and safety: a perspective review. Ther Adv Drug Saf. 2014 Dec;5(6):242-54. doi: 10.1177/2042098614551938.
• Background EMA confirms recommendations to minimise ketoacidosis risk with SGLT2 inhibitors for diabetes 2016. www.ema.europe.eu.
• Background Frias JP, Guja C, Hardy E, Ahmed A, Dong F, Ohman P, Jabbour SA. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2016 Dec;4(12):1004-1016. doi: 10.1016/S2213-8587(16)30267-4. Epub 2016 Sep 16.
• Background FDA approves Farxiga to treat type 2 diabetes. 2014 n.d. fda.gov.
• Background FDA Approves Bydureon Pen. 2014 n.d. drugs.com.

Drugs

Indications