T-1095

T-1095 is a potent and selective inhibitor of Na+-glucose cotransporters (SGLTs). T-1095 may be a useful antidiabetic drug. Long-term treatment with T-1095 causes sustained improvement in hyperglycemia and prevents diabetic neuropathy in Goto-Kakizaki Rats. Chronic administration of T-1095 (0.1% w w(-1) pellet chow, for 12 weeks) decreased blood glucose and haemoglobin A(1C) levels, and improved glucose intolerance in db/db mice. The age-related decrease in plasma insulin levels was markedly inhibited and there was a 2.5 fold increase of insulin content in the pancreas of T-1095-treated db/db mice. T-1095 improved the metabolic abnormalities and inhibit the development of diabetic complications in db/db mice.

1: Yamaguchi K, Kato M, Ozawa K, Kawai T, Yata T, Aso Y, Ishigai M, Ikeda S. Pharmacokinetic and pharmacodynamic modeling for the effect of sodium-glucose cotransporter inhibitors on blood glucose level and renal glucose excretion in db/db mice. J Pharm Sci. 2012 Nov;101(11):4347-56. doi: 10.1002/jps.23302. Epub 2012 Aug 23. PubMed PMID: 22927193.

2: Nomura S, Sakamaki S, Hongu M, Kawanishi E, Koga Y, Sakamoto T, Yamamoto Y, Ueta K, Kimata H, Nakayama K, Tsuda-Tsukimoto M. Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus. J Med Chem. 2010 Sep 9;53(17):6355-60. doi: 10.1021/jm100332n. PubMed PMID: 20690635.