Inhibition of SGLT2: A novel strategy for treatment of type 2 diabetes mellitus

Clinical Pharmacology and Therapeutics

Volumn 89, Issue 4, 2011, Pages 621-625

  Pfister, M ^a   Whaley, J M ^a   Zhang, L ^a   List, J F ^a  

^a BRISTOL MYERS SQUIBB RESEARCH AND DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDIABETIC AGENT; ASP 1941; BI 10773; CANAGLIFLOZIN; DAPAGLIFLOZIN; GLUCOSE; HEMOGLOBIN A1C; INSULIN; LX 4211; METFORMIN; ORAL ANTIDIABETIC AGENT; PHLORIZIN; PLACEBO; SODIUM GLUCOSE COTRANSPORTER 1; SODIUM GLUCOSE COTRANSPORTER 2; SULFONYLUREA; UNCLASSIFIED DRUG;

ADD ON THERAPY; AMINO ACID SEQUENCE; AREA UNDER THE CURVE; ARTICLE; CALORIC INTAKE; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; EXERCISE; GLUCOSE BLOOD LEVEL; GLUCOSE URINE LEVEL; GLUCOSURIA; GLYCEMIC CONTROL; HUMAN; HYPERGLYCEMIA; INSULIN SENSITIVITY; MONOTHERAPY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; TREATMENT RESPONSE; URINARY EXCRETION; WEIGHT REDUCTION;

ANIMALS; DIABETES MELLITUS, TYPE 2; DRUG DESIGN; GLUCOSE; HUMANS; HYPOGLYCEMIC AGENTS; MODELS, ANIMAL; SODIUM-GLUCOSE TRANSPORTER 2;

EID: 79952991904     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/clpt.2011.16     Document Type: Article

References (40)

1. Wright, E.M. & Turk, E. The sodium/glucose cotransport family SLC5. Pflugers Arch. 447, 510-518 (2004). (Pubitemid 38241437)
2. Martín, M.G., Turk, E., Lostao, M.P., Kerner, C. & Wright, E.M. Defects in Na+/ glucose cotransporter (SGLT1) trafficking and function cause glucosegalactose malabsorption. Nat. Genet. 12, 216-220 (1996). (Pubitemid 26051306)
3. Santer, R. & Calado, J. Familial renal glucosuria and SGLT2: from a Mendelian trait to a therapeutic target. Clin. J. Am. Soc. Nephrol. 5, 133-141 (2010).
4. Chen, J. et al. Quantitative pCR tissue expression profiling of the human SGLT2 gene and related family members. Diabetes Ther., In press.
5. Hummel, C.S., Lu, C., Loo, D.D., Hirayama, B.A., Voss, A.A. & Wright, E.M. Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am. J. Physiol., Cell Physiol. 300, C14-C21 (2011).
6. Achard, C. & Delamare, V. The bark of the apple root, Phlorizin, Reduces diabetic hyperglycemia. Soc. Med. Des. Hopitaux. 379-393 (1899).
7. Rossetti, L., Smith, D., Shulman, G.I., Papachristou, D. & DeFronzo, R.A. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J. Clin. Invest. 79, 1510-1515 (1987). (Pubitemid 17099657)
8. Washburn, W.N. Evolution of sodium glucose co-transporter 2 inhibitors as anti-diabetic agents. Expert Opin. Ther. Pat. 19, 1485-1499 (2009).
9. Jurczak, M.J. et al. SGLT2 deletion improves glucose homeostasis and preserves pancreatic ?-cell function. Diabetes, In press.
10. Obermeier, M. et al. In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), A potent sodium-glucose cotransporter type ii inhibitor, In animals and humans. Drug Metab. Dispos. 38, 405-414 (2010).
11. Han, S. et al. Dapagliflozin, A selective SGLT2 inhibitor, Improves glucose homeostasis in normal and diabetic rats. Diabetes 57, 1723-1729 (2008).
12. Macdonald, F.R. et al. The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, Diabetic rats. Diabetes. Obes. Metab. 12, 1004-1012 (2010).
13. Nawano, M. et al. Hyperglycemia contributes insulin resistance in hepatic and adipose tissue but not skeletal muscle of ZDF rats. Am. J. Physiol. Endocrinol. Metab. 278, E535-E543 (2000). (Pubitemid 30149399)
14. Fujimoto, Y., Torres, T.P., Donahue, E.P. & Shiota, M. Glucose toxicity is responsible for the development of impaired regulation of endogenous glucose production and hepatic glucokinase in Zucker diabetic fatty rats. Diabetes 55, 2479-2490 (2006). (Pubitemid 44871148)
15. Rossetti, L., Shulman, G.I., Zawalich, W. & DeFronzo, R.A. Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats. J. Clin. Invest. 80, 1037-1044 (1987). (Pubitemid 18075639)
16. Wilding, J.P., Norwood, P., T'joen, C., Bastien, A., List, J.F. & Fiedorek, F.T. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care 32, 1656-1662 (2009).
17. Bailey, C.J., Gross, J.L., Pieters, A., Bastien, A. & List, J.F. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, Double-blind, Placebo-controlled trial. Lancet 375, 2223-2233 (2010).
18. Ferrannini, E., Ramos, S.J., Salsali, A., Tang, W. & List, J.F. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, Double-blind, Placebo-controlled, Phase 3 trial. Diabetes Care 33, 2217-2224 (2010).
19. Strojek, K., Hruba, V., Elze, M., Langkilde, A. & Parikh, S. Efficacy and safety of dapagliflozin in patients with type 2 diabetes mellitus and inadequate glycaemic control on glimepride monotherapy [Abstract]. Diabetologia 53(suppl. 1), S347 (2010).
20. Vallon, V. et al. SGLT2 mediates glucose reabsorption in the early proximal tubule. J. Am. Soc. Nephrol. 22, 104-112 (2011).
21. Komoroski, B. et al. Dapagliflozin, A novel SGLT2 inhibitor, Induces dosedependent glucosuria in healthy subjects. Clin. Pharmacol. Ther. 85, 520-526 (2009).
22. 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. 85, 513-519 (2009).
23. Wright, E.M., Hirayama, B.A. & Loo, D.F. Active sugar transport in health and disease. J. Intern. Med. 261, 32-43 (2007). (Pubitemid 46046470)
24. List, J.F., Woo, V., Morales, E., Tang, W. & Fiedorek, F.T. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 32, 650-657 (2009).
25. Zhang, L., Feng, Y., List, J., Kasichayanula, S. & Pfister, M. Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight. Diabetes. Obes. Metab. 12, 510-516 (2010).
26. Wilding, J.P.H., Woo, V., Soler, N.G., Pahor, A., Sugg, J. & Parikh, S. Sustained effectiveness of dapagliflozin over 48 weeks in patients with type 2 diabetes poorly controlled with insulin [Abstract]. Diabetes 59(suppl. 1a, P.LB7) (2010).
27. Zhang, L., Ng, C.M., List, J.F. & Pfister, M. Synergy between scientific advancement and technological innovation, Illustrated by a mechanismbased model characterizing sodium-glucose cotransporter-2 inhibition. J. Clin. Pharmacol. 50, 113S-120S (2010).
28. Kurosaki, E. et al. In vitro and in vivo pharmacological properties of aSp1941, A novel, Potenet and selective SGLT2 inhibitor [Abstract]. Diabetes 59(suppl. 1), A156 (2010).
29. Schwartz, S., Klasen, S., Kowalski, D. & Akinlade, B. ASp1941, A novel and selective inhibitor of sodium-glucose co-transporter 2 (SGLT2), Reduces fasting plasma glucose in patients with type 2 diabetes mellitus [Abstract]. Diabetes 59(suppl. 1), A154 (2010).
30. Kashiwagi, A., Utsuno, A., Kazuta, K., Yoshida, S. & Kageyama, S. ASp1941, A novel, Selective SGLT2 inhibitor, Was effective and safe in Japanese healthy volunteers and patients with type 2 diabetes mellitus [Abstract]. Diabetes 59 (suppl. 1), A21 (2010).
31. Veltkamp, S.A., Kadokura, T., Krauwinkel, W.J.J. & Smulders, R.A. ASp1941, A novel and selective SGLT2 inhibitor, Stimulates urinary glucose excretion in healthy subjects [Abstract]. Diabetes 59(suppl. 1), A154 (2010).
32. Grempler, R. et al. In vitro properties and in vivo effect on urinary glucose excretion of Bi 10773, A novel selective SGLT2 inhibitor [Abstract]. Diabetes 58(suppl. 1), A469 (2009).
33. Heise, T. et al. Bi 10773, A sodium-glucose co-transporter inhibitor (SGLT-2), Is safe and efficacious following 4-week treatment in patients with type 2 diabetes [Abstract]. Diabetes 59(suppl. 1), A172 (2010).
34. Seman, L. et al. Safety and tolerability of Bi 10773, A sodium glucose cotransporter-2 (SGLT-2) inhibitor, Following 8-days treatment in patients with type 2 diabetes [Abstract]. Diabetes 59(suppl. 1), A156 (2010).
35. Port, A. et al. Safety, Tolerability, Pharmacokinetics and pharmacodynamics of Bi 10773, A sodium-glucose co-transporter inhibitor (SGLT-2), In healthy volunteers [Abstract]. Diabetes 59(suppl. 1), A155 (2010).
36. Nomura, S. et al. 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. 53, 6355-6360 (2010).
37. Schwartz, S. et al. Canagliflozin improves glycemic control in subjects with type 2 diabetes (T2D) not optimally controlled on stable doses of insulin [Abstract]. Diabetes 59(suppl. 1), A154 (2010).
38. Sha, S. et al. Canagliflozin, A novel inhibitor of sodium glucose co-transporter 2, Improved glucose control in subjects with type 2 diabetes and was well tolerated [Abstract]. Diabetes 59(suppl. 1), A155 (2010).
39. Meng, W. et al. Discovery of dapagliflozin: a potent, Selective renal sodiumdependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J. Med. Chem. 51, 1145-1149 (2008). (Pubitemid 351480378)
40. Freiman, J. et al. LX4211, A dual SGLT2/SGLT1 inhibitor, Shows rapid and significant improvement in glycemic control over 28 days in patients with type 2 diabetes (T2DM) [Abstract]. Diabetes 59(suppl. 1), LB5-LB6 (2010).