First human dose-escalation study with remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2 (SGLT2), in healthy subjects and in subjects with type 2 diabetes mellitus

BMC Pharmacology and Toxicology

Volumn 14, Issue , 2013, Pages

  Kapur, Anita ^a   O'Connor Semmes, Robin ^a   Hussey, Elizabeth K ^a   Dobbins, Robert L ^a   Tao, Wenli ^a   Hompesch, Marcus ^b   Smith, Glenn A ^a   Polli, Joseph W ^a   James, Charles D ^c   Mikoshiba, Imao ^d   Nunez, Derek J ^a  

^a GLAXOSMITHKLINE   (United States)

^b Profil Institute for Clinical Research   (United States)

^c Tandem Labs   (United States)

^d KISSEI PHARMACEUTICAL CO LTD   (Japan)

Author keywords

Pharmacodynamics; Pharmacokinetics; Remogliflozin etabonate; Sodium dependent glucose transporter 2 inhibitor; Type 2 diabetes mellitus

Indexed keywords

GLUCOSE; INSULIN; PLACEBO; REMOGLIFLOZIN ETABONATE; ANTIDIABETIC AGENT; ELECTROLYTE; GLUCOSE BLOOD LEVEL; GLUCOSIDE; PYRAZOLE DERIVATIVE; SLC5A2 PROTEIN, HUMAN; SODIUM GLUCOSE COTRANSPORTER 2;

ADULT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG DOSE ESCALATION; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; GLUCOSE BLOOD LEVEL; HUMAN; INSULIN BLOOD LEVEL; MALE; MAXIMUM PLASMA CONCENTRATION; NON INSULIN DEPENDENT DIABETES MELLITUS; ORAL GLUCOSE TOLERANCE TEST; PHARMACODYNAMICS; RANDOMIZED CONTROLLED TRIAL; TIME TO MAXIMUM PLASMA CONCENTRATION; ANTAGONISTS AND INHIBITORS; BLOOD; CHEMICAL STRUCTURE; CHEMICALLY INDUCED; DIABETES MELLITUS, TYPE 2; DIARRHEA; DIZZINESS; HEADACHE; METABOLIC CLEARANCE RATE; METABOLISM; MIDDLE AGED; TREATMENT OUTCOME; URINE;

ADULT; AREA UNDER CURVE; BLOOD GLUCOSE; CROSS-OVER STUDIES; DIABETES MELLITUS, TYPE 2; DIARRHEA; DIZZINESS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; ELECTROLYTES; FEMALE; GLUCOSIDES; HEADACHE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; MOLECULAR STRUCTURE; PYRAZOLES; SODIUM-GLUCOSE TRANSPORTER 2; TREATMENT OUTCOME;

EID: 84880643826     PISSN: 20506511     EISSN: None     Source Type: Journal    
DOI: 10.1186/2050-6511-14-26     Document Type: Article

References (26)

1. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008, 359:1577-1589.
2. UK Prospective Diabetes Study (UKPDS) Group Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998, 352:854-865. UK Prospective Diabetes Study (UKPDS) Group.
3. Giugliano D, Standl E, Vilsboll T, Betteridge J, Bonadonna R, Campbell I, Schernthaner G, Staels B, Trichopoulou A, Farinaro E. Is the current therapeutic armamentarium in diabetes enough to control the epidemic and its consequences? What are the current shortcomings?. Acta Diabetol 2009, 46:173-181.
4. Kanai Y, Lee WS, You G, Brown D, Hediger MA. The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Invest 1994, 93:397-404.
5. Wells RG, Pajor AM, Kanai Y, Turk E, Wright EM, Hediger MA. Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter. Am J Physiol 1992, 263:F459-F465.
6. You G, Lee WS, Barros EJ, Kanai Y, Huo T, Khawaja S, Wells R, Nigam S, Hediger M. Molecular characteristics of Na(+)-coupled glucose transporters in adult and embryonic rat kidney. J Biol Chem 1995, 270:29365-29371.
7. Bakris GL, Fonseca VA, Sharma K, Wright EM. Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int 2009, 75:1272-1277.
8. Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human ATP-binding cassette and solute carrier transporter superfamilies. Drug Metab Pharmacokinet 2005, 20:452-477.
9. Idris I, Donnelly R. Sodium-glucose co-transporter-2 inhibitors: an emerging new class of oral antidiabetic drug. Diabetes Obes Metab 2009, 11:79-88.
10. Wright EM, Turk E. The sodium/glucose cotransport family SLC5. Pflugers Arch 2004, 447:510-518.
11. Santer R, Kinner M, Lassen CL, Schneppenheim R, Eggert P, Bald M, Brodehl J, Daschner M, Ehrich J, Kemper M, Li Volti S, Neuhaus T, Skovby F, Swift P, Schaub J, Klaerke D. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J Am Soc Nephrol 2003, 14:2873-2882.
12. Handlon AL. Sodium glucose co-transporter 2 (SGLT2) inhibitors as potential antidiabetic agents. Expert Opin Ther Pat 2005, 13:1531-1540.
13. Hussey E, Clark R, Amin D, Kipnes M, O'Connor-Semmes R, O'Driscoll E, Leong L, Murray S, Dobbins R, Layko D, Nunez D. The single-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a novel inhibitor of glucose reabsorption, in healthy volunteers and subjects with type 2 diabetes mellitus. J Clin Pharmacol 2010, 50:623-635.
14. Isaji M. Sodium-glucose cotransporter inhibitors for diabetes. Curr Opin Investig Drugs 2007, 8:285-292.
15. Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther 2009, 85:513-519.
16. Komoroski B, Vachharajani N, Boulton D, Kornhauser D, Geraldes M, Li L, Pfister M. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Ther 2009, 85:520-526.
17. Asano T, Ogihara T, Katagiri H, Sakoda H, Ono H, Fujishiro M, Anai M, Kurihara H, Uchijima Y. Glucose transporter and Na+/glucose cotransporter as molecular targets of anti-diabetic drugs. Curr Med Chem 2004, 11:2717-2724.
18. Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab Res Rev 2005, 21:31-38.
19. Katsuno K, Fujimori Y, Takemura Y. Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level. J Pharmacol Exp Ther 2007, 320:323-330.
20. Fujimori Y, Katsuno K, Nakashima I, Ishikawa-Takemura Y, Fujikura H, Isaji M. Remogliflozin etabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther 2008, 327:268-276.
21. Harrington WW, Milliken NO, Binz JG. Remogliflozin etabonate, a potent and selective sodium-dependent glucose transporter 2 antagonist, produced sustained metabolic effects in zucker diabetic fatty rats. Diabetes 2008, 58:529-P.
22. Wright EM, Turk E, Martin MG. Molecular basis for glucose-galactose malabsorption. Cell Biochem Biophys 2002, 36:115-121.
23. Sigafoos J, Bowers G, Castellino S, Culp AG, Wagner DS, Reese JM, Humphreys JE, Hussey EK, O'Connor-Semmes RL, Kapur A, Tao W, Dobbins RL, Polli JW. Assessment of the drug interaction risk for remogliflozin etabonate, a sodium-dependent glucose cotransporter-2 inhibitor: evidence from in vitro, human mass balance, and ketoconazole interaction studies. Drug Metab Dispos 2012, 40:1-13.
24. Yabe D, Watanabe K, Sugawara K, Kuwata H, Kitamoto Y, Sugizaki K, Fujiwara S, Hishizawa M, Hyo T, Kuwabara K, Yokota K, Iwasaki M, Kitatani N, Kurose T, Inagaki N, Seino Y. Comparison of incretin immunoassays with or without plasma extraction: Incretin secretion in Japanese patients with type 2 diabetes. J Diabetes Investig 2012, 3:70-79.
25. Deacon CF, Holst JJ, Sugawara K. Immunoassays for the incretin hormones GIP and GLP-1. Best Pract Res Clin Endocrinol Metab 2009, 23(4):425-462. ISSN 1521-690X, 10.1016/j.beem.2009.03.006. [http://www.sciencedirect.com/science/article/pii/S1521690X09000256].
26. O'Connor-Semmes R, Hussey EK, Dobbins RL, Nunez DJ. Simulation and prediction of long-term clinical efficacy in type 2 diabetes resulting from inhibition of the renal sodium-glucose cotransporter 2 (SGLT2). Diabetes 2008, 57(2132-PO):A589.