Saxagliptin in Combination With Dapagliflozin - Effects on Islet Cell Function

Summary

The purpose of this study is to evaluate alpha- and beta-cell function during combination treatment with saxagliptin in addition to dapagliflozin and metformin compared to placebo in addition to dapagliflozin and metformin in subjects with T2DM on stable metformin background therapy.

Timeline

Start

2015-01

Primary completion

2016-08

Completion

2016-08

Publications

• Results List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care. 2009 Apr;32(4):650-7. doi: 10.2337/dc08-1863. Epub 2008 Dec 29.
• Results Rosenstock J, Vico M, Wei L, Salsali A, List JF. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care. 2012 Jul;35(7):1473-8. doi: 10.2337/dc11-1693. Epub 2012 Mar 23.
• Results Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q, Tomiyama H, Kobayashi Y, Noda A, Sasamata M, Shibasaki M. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol. 2013 Sep 5;715(1-3):246-55. doi: 10.1016/j.ejphar.2013.05.014. Epub 2013 May 23.
• Results Chen L, Klein T, Leung PS. Effects of combining linagliptin treatment with BI-38335, a novel SGLT2 inhibitor, on pancreatic islet function and inflammation in db/db mice. Curr Mol Med. 2012 Sep;12(8):995-1004. doi: 10.2174/156652412802480970.
• Results Kurosaki E, Ogasawara H. Ipragliflozin and other sodium-glucose cotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes: preclinical and clinical data. Pharmacol Ther. 2013 Jul;139(1):51-9. doi: 10.1016/j.pharmthera.2013.04.003. Epub 2013 Apr 4.
• Results Forst T, Dworak M, Berndt-Zipfel C, Loffler A, Klamp I, Mitry M, Pfutzner A. Effect of vildagliptin compared to glimepiride on postprandial proinsulin processing in the beta cell of patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2013 Jun;15(6):576-9. doi: 10.1111/dom.12063. Epub 2013 Feb 6.
• Results Forst T, Anastassiadis E, Diessel S, Loffler A, Pfutzner A. Effect of linagliptin compared with glimepiride on postprandial glucose metabolism, islet cell function and vascular function parameters in patients with type 2 diabetes mellitus receiving ongoing metformin treatment. Diabetes Metab Res Rev. 2014 Oct;30(7):582-9. doi: 10.1002/dmrr.2525.
• Results Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, Broedl UC, Woerle HJ. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014 Feb;124(2):499-508. doi: 10.1172/JCI72227. Epub 2014 Jan 27.
• Results Merovci A, Solis-Herrera C, Daniele G, Eldor R, Fiorentino TV, Tripathy D, Xiong J, Perez Z, Norton L, Abdul-Ghani MA, DeFronzo RA. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014 Feb;124(2):509-14. doi: 10.1172/JCI70704. Epub 2014 Jan 27.
• Results Zhang Y, Chi J, Wang W, Hong J, Gu W, Wang B, Ning G. Different effects of two dipeptidyl peptidase-4 inhibitors and glimepiride on beta-cell function in a newly designed two-step hyperglycemic clamp. J Diabetes. 2015 Mar;7(2):213-21. doi: 10.1111/1753-0407.12175. Epub 2014 Jul 29.
• Results McGuire EA, Helderman JH, Tobin JD, Andres R, Berman M. Effects of arterial versus venous sampling on analysis of glucose kinetics in man. J Appl Physiol. 1976 Oct;41(4):565-73. doi: 10.1152/jappl.1976.41.4.565.
• Results Liu D, Moberg E, Kollind M, Lins PE, Adamson U, Macdonald IA. Arterial, arterialized venous, venous and capillary blood glucose measurements in normal man during hyperinsulinaemic euglycaemia and hypoglycaemia. Diabetologia. 1992 Mar;35(3):287-90. doi: 10.1007/BF00400932.
• Results Cobb J, Gall W, Adam KP, Nakhle P, Button E, Hathorn J, Lawton K, Milburn M, Perichon R, Mitchell M, Natali A, Ferrannini E. A novel fasting blood test for insulin resistance and prediabetes. J Diabetes Sci Technol. 2013 Jan 1;7(1):100-10. doi: 10.1177/193229681300700112.

Drugs

Indications