SGLT2 inhibitors: A promising new therapeutic option for treatment of type 2 diabetes mellitus

Journal of Pharmacy and Pharmacology

Volumn 65, Issue 3, 2013, Pages 317-327

  Misra, Monika ^a  

^a ALIGARH MUSLIM UNIVERSITY   (India)

Author keywords

glycosuria; sodium glucose co transporters; type 2 diabetes mellitus

Indexed keywords

ANTIDIABETIC AGENT; ANTISENSE OLIGONUCLEOTIDE; CANAGLIFLOZIN; DAPAGLIFLOZIN; EMPAGLIFLOZIN; ERTUGLIFLOZIN; GLIPIZIDE; GLUCOSE; HEMOGLOBIN A1C; INSULIN; IPRAGLIFLOZIN; ISIS 388626; ISIS 388629; LUSEOGLIFLOZIN; LX 4211; MAGNESIUM; METFORMIN; NITROGEN; ORAL ANTIDIABETIC AGENT; PF 4971729; PHOSPHATE; PHOSPHORUS; PLACEBO; REMOGLIFLOZIN; SERGIFLOZIN; SODIUM GLUCOSE COTRANSPORTER 1; SODIUM GLUCOSE COTRANSPORTER 2; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; TOFOGLIFLOZIN; TS 071; UNCLASSIFIED DRUG; UNINDEXED DRUG; UREA; URIC ACID;

ANTIDIABETIC ACTIVITY; AREA UNDER THE CURVE; BLADDER CANCER; BREAST CANCER; CELL MEMBRANE TRANSPORT; DIABETIC NEPHROPATHY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG WITHDRAWAL; GENITAL TRACT INFECTION; GLUCOSE BLOOD LEVEL; GLUCOSE TRANSPORT; GLYCEMIC CONTROL; HEMATOCRIT; HUMAN; HYPOGLYCEMIA; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIVER TOXICITY; MAGNESIUM BLOOD LEVEL; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PHOSPHATE BLOOD LEVEL; PROTEIN FUNCTION; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; UREA NITROGEN BLOOD LEVEL; URIC ACID BLOOD LEVEL; URINARY TRACT INFECTION; WEIGHT REDUCTION;

ANIMALS; DIABETES MELLITUS, TYPE 2; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIC AGENTS; SODIUM-GLUCOSE TRANSPORTER 2;

EID: 84873079417     PISSN: 00223573     EISSN: 20427158     Source Type: Journal    
DOI: 10.1111/j.2042-7158.2012.01574.x     Document Type: Review

References (76)

1. L'Abbate A,. Large and micro coronary vascular involvement in diabetes. Pharmacol Rep 2005; 57 (Suppl.): 3-9.
2. Kaiser N, et al,. Glucotoxicity and beta-cell failure in type 2 diabetes mellitus. J Pediatr Endocrinol Metab 2003; 16: 5-22.
3. Prentki M, Nolan CJ,. Islet beta cell failure in type 2 diabetes. J Clin Invest 2006; 116: 1802-1812.
4. Inzucchi SE,. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002; 287: 360-372.
5. Wood IS, Trayhurn P,. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 2003; 89: 3-9.
6. Uldry M, Thorens B,. The SLC2 family of facilitated hexose and polyol transporters. Pflugers Arch 2004; 447: 480-489.
7. Nair S, Wilding JP,. Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab 2010; 95: 34-42.
8. Wright EM, Turk E,. The sodium/glucose cotransport family SLC5. Pflugers Arch 2004; 447: 510-518.
9. Kanai Y, et al,. 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.
10. Chao EC, Henry RR,. SGLT2 inhibition-a novel strategy for diabetes treatment. Nat Rev Drug Discov 2010; 9: 551-559.
11. Martín MG, et al,. Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactosemalabsorption. Nat Genet 1996; 12: 216-220.
12. Turk E, et al,. Structure of the human Na+/glucose cotransporter gene SGLT1. J Biol Chem 1994; 269: 15204-15209.
13. Shibazaki T, et al,. KGA-2727, a novel selective inhibitor of high-affinity sodium glucose cotransporter (SGLT1), exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther 2012; 342: 288-296.
14. ClinicalTrails.gov. A 2-Part trial in subjects with type 2 diabetes and in healthy subjects to evaluate GSK1614235, a new glucose lowering drug to treat type 2 diabetes (SGA112534). 2011. Available from: http://clinicaltrials.gov/ ct2/show/NCT00976261.
15. 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. Diabetes 2010; 59 (Suppl. 1A): LB5. (Abstract 17LB).
16. Abdul-Ghani MA, et al,. Efficacy and safety of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus. Curr Diab Rep 2012; 12: 230-238.
17. van den Heuvel LP, et al,. Autosomal recessive renal glycosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2). Hum Genet 2002; 111: 544-547.
18. Santer R, et al,. Molecular analysis of the SGLT2 gene in patients with renal glycosuria. J Am Soc Nephrol 2003; 14: 2873-2882.
19. Elsas LJ, et al,. Autosomal recessive inheritance of renal glycosuria. Metabolism 1971; 20: 968-975.
20. Elsas LJ, Rosenberg LE,. Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine. J Clin Invest 1969; 48: 1845-1845.
21. Calado J, et al,. Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glycosuria. Hum Genet 2004; 114: 314-316.
22. Oemar BS, et al,. Complete absence of tubular glucose reabsorption: a new type of renal glycosuria (type 0). Clin Nephrol 1987; 27: 156-160.
23. Dominguez JH, et al,. Molecular adaptations of GLUT1 and GLUT2 in renal proximal tubules of diabetic rats. Am J Physiol 1994; 266: (2 Pt 2) F283-F290.
24. Freitas HS, et al,. Na (+) -glucose transporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1alpha expression and activity. Endocrinology 2008; 149: 717-724.
25. Rahmoune H, et al,. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 2005; 54: 3427-3434.
26. Jabbour SA, Goldstein BJ,. Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes. Int J Clin Pract 2008; 62: 1279-1284.
27. Han S, et al,. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes 2008; 57: 1723-1729.
28. Boldys A, Okopien B,. Inhibitors of type 2 sodium glucose co-transporters-a new strategy for diabetes treatment. Pharmacol Rep 2009; 61: 778-784.
29. Kahn BB, et al,. Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression. J Clin Invest 1991; 87: 561-570.
30. Bailey CJ, et al,. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet 2010; 375: 2223-2233.
31. Kipnes MS,. Sodium-glucose cotransporter 2 inhibitors in the treatment of type 2 diabetes: a review of phase II and III trials. Clin. Invest 2010; 1: 145-156.
32. Strojek K, et al,. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomised, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab 2011; 13: 928-938.
33. Wilding JPH, et al,. Dapagliflozin in patients with type 2 diabetes poorly controlled on insulin therapy-efficacy of a novel insulin-independent treatment. Diabetes 2010; 59 (Suppl. 1): A21-A22. (Abstract 78-OR).
34. Nauck MA, et al,. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled non-inferiority trial. Diabetes Care 2011; 34: 2015-2022.
35. Ferrannini E, et al,. Dapagliflozinmonotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 2010; 33: 2217-2224.
36. Bristol Myers Squibb company (research and development). Dapagliflozin-Background document. BMS 512148. NDA 202292 (cited on: July 19, 2011). Available from: http://www.fda.gov/downloads/AdvisoryCommittees/ CommitteesMeetingMaterials/Drugs/ EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM262996.pdf (last accessed on: February 7, 2012).
37. Meyers JL, et al,. Type 2 diabetes mellitus and renal impairment in a large outpatient electronic medical records database: rates of diagnosis and antihyperglycemic medication dose adjustment. Postgrad Med 2011; 123: 133-143.
38. FDAAdvisory Committee Meeting. FDA briefing document. NDA 202293. (Dapagliflozin tablets 5 mg and 10 mg. Sponsor: Bristol Myers Squibb) (cited on: July 19, 2011). Available from: http://www.fda.gov/downloads/ AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM262994.pdf (last accessed on: February 7, 2012).
39. Ehrenkranz JR, et al,. Phlorizin: a review. Diabetes Metab Res Rev 2005; 21: 31-38.
40. Rossetti L, et al,. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 1987; 79: 1510-1515.
41. Oku A, et al,. T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes 1999; 48: 1794-1800.
42. Isaji M,. SGLT2 inhibitors: molecular design and potential differences in effect. Kidney Int Suppl 2011; 79 (Suppl. 120): S14-S19.
43. Hussey EK, et al,. Single-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a novel inhibitor of glucose reabsorption, in healthy volunteers and patients with type 2 diabetes mellitus. J Clin Pharmacol 2010; 50: 623-635.
44. Hussey EK, et al,. Multiple-dose pharmacokinetics and pharmacodynamics of sergliflozinetabonate, a novel inhibitor of glucose reabsorption, in healthy overweight and obese subjects: a randomized double-blind study. J Clin Pharmacol 2010; 50: 636-646.
45. th Scientific Session of American Diabetes Association 2009 June 5-9; New Orleans, LA. (Abstract 573-P). Available from: http://professional.diabetes.org/Abstracts-Display.aspx? TYP=1&CID=73295 (last accessed on: July 29, 2012).
46. Meng W, et al,. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem 2008; 51: 1145-1149.
47. List JF, et al,. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 2009; 32: 650-657.
48. Wilding JP, et al,. 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 2009; 32: 1656-1662.
49. Komoroski B, et al,. 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.
50. Nauck M, et al,. Long-term efficacy and safety of add-on dapagliflozin vs add-on glipizide in patients with T2DM inadequately controlled with metformin: 2-year results. Diabetes 2011; 60 (Suppl. 1A): LB12. (Abstract-40 LB).
51. Irony I,. FDA advisory committee meeting (cited on: 19 July, 2011). Available from: http://www.fda.gov/downloads/AdvisoryCommittees/ CommitteesMeetingMaterials/Drugs/ EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM264312.pdf (last accessed on: February 7, 2012).
52. Jones D,. Diabetes field cautiously upbeat despite possible setback for leading SGLT2 inhibitor. Nat Rev Drug Discov 2011; 10: 645-646.
53. Musso G, et al,. A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors. Systematic review and meta-analysis of randomized trials. Ann Med 2012; 44: 375-393.
54. Golembiewska E, et al,. Renal handling of uric acid in patients with type 1 diabetes in relation to glycemic control. Arch Med Res 2005; 36: 32-35.
55. Pollack A,. Diabetes Drug Dapagliflozin Rejected by FDA. The New York Times (published on: July 19, 2011). Available from: http://www.nytimes.com/ 2011/07/20/business/diabetes-drug-dapagliflozin-rejected-by-fda-panel.html (last accessed on: February 7, 2012).
56. Pollack A,. FDA Delays Approval of New Diabetes Drug. The New York Times prescription blog (cited on: January 19, 2012). Available from: http://prescriptions.blogs.nytimes.com/ (last accessed on: February 7, 2012).
57. Forxiga. European Medicines Agency (cited on: April 19, 2012). Available from: http://www.ema.europa.eu/docs/en-GB/document-library/Summary-of-opinion- Initial-authorisation/human/002322/WC500125684.pdf (last accessed on: July 29, 2012).
58. Johnson & Johnson. Janssen Research & Development Submits New Drug Application to U.S. FDA for Canagliflozin to Treat Patients with Type 2 Diabetes (cited on: May 31, 2012). Available from: http://www.jnj.com/connect/ news/all/janssen-research-development-submits-new-drug-application-to-us-fda- for-canagliflozin-to-treat-patients-with-type-2-diabetes (last accessed on: June 9, 2012).
59. Boehringer Ingelheim. R & D Pipeline (cited on: June 4, 2012). Available from: http://www.boehringer-ingelheim.com/research-development/drug- discovery/pipeline.html (last accessed on: June 9, 2012).
60. Astella Pharma Inc. R& D pipeline (cited in May 2012). Available from: http://www.astellas.com/en/ir/library/pdf/library20120511-en.ZIP (last accessed on: June 9, 2012).
61. Lexicon Pharmaceuticals. Drug pipeline. Available from: http://www.lexgen.com/pipeline/index.html (last accessed on June 9, 2012).
62. Taisho Pharmaceuticals Co. Ltd. New drug pipeline. Available from: http://www.taisho-holdings.co.jp/en/ir/development/ (last accessed on: June 9, 2012).
63. Chugai pharmaceuticals Co. Ltd. Development pipeline. Available from: http://www.chugai-pharm.co.jp/hc/ss/english/ir/reports-downloads/pipeline. html#table04 (last accessed on: July 29, 2012).
64. Pfizer. Pipeline (cited on: May 10, 2012). Available from: http://www.pfizer.com/files/research/pipeline/2012-0510/pipeline-2012-0510.pdf (last accessed on: July 29, 2012).
65. ClinicalTrial.gov (last updated on July 21, 2011). Safety, Tolerability and Pharmacokinetics Study of EGT0001474 in Subjects With Type 2 Diabetes. Available from: http://clinicaltrials.gov/ct2/show/NCT00924053?term= EGT0001474&rank=2 (last accessed on: July 29, 2012).
66. ClinicalTrials.gov. Safety, Tolerability and Activity Study of Multiple Doses of ISIS-SGLT2Rx in Healthy Volunteers. NCT00836225 (Sponsor: Isis Pharmaceuticals) (cited on: February 2, 2009). Available from: http://clinicaltrials.gov/ct2/show/NCT00836225 (last accessed on: February 7, 2012).
67. Devineni D, et al,. Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin. Diabetes Obes Metab 2012; 14: 539-545.
68. th Scientific Session of American Diabetes Association 2010 June 25-29; Orlando, FL. (Abstract 77-OR). Available from: http://professional. diabetes.org/Abstracts-Display.aspx?TYP=1&CID=79023 (last accessed on: July 29, 2012).
69. Inagaki N, et al,. Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2 (SGLT2) improves glycemic control and reduces body weight in Japanese type 2 diabetes mellitus (T2DM). Diabetes 2011; 60 (Suppl. 1): A274. (Abstract 999-P).
70. Rosenstock J, et al,. Efficacy and safety of BI 10773, a new sodium glucose cotransporter-2 (SGLT-2) inhibitor, in type 2 diabetes inadequately controlled on metformin. Diabetes 2011; 60 (Suppl. 1): A271. (Abstract 989-P).
71. Ferrannini E, et al,. The potent and highly selective sodium glucose co transporter-2 (SGLT2) inhibitor BI 10773 is safe and efficacious monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2010; 53 (Suppl. 1): S351. (Abstract 877).
72. th Scientific Session of American Diabetes Association 2010 June 25-29; Orlando, FL. (Abstract: 75-OR). Available from: http://professional.diabetes.org/Adv-SearchResult.aspx?congress= 116&tit=75%20OR&spk=&ses=&kwd=ASP1941&cgr=116&typ=10 (last accessed on: July 29, 2012).
73. Kashiwagi A, et al,. Ipragliflozin improved glycaemic control with additional benefits of reductions of body weight and blood pressure in Japanese patients with type 2 diabetes mellitus: BRIGHTEN Study. Diabetologia 2011; 54 (Suppl. 1): S68. (Abstract 149).
74. Seino Y, et al,. TS-071, a novel and selective SGLT2 inhibitor, improved glycemic control and decreased body weight in 12-week study of Japanese patients with type 2 diabetes mellitus. Diabetes 2011; 60 (Suppl. 1): A274. (Abstract 998-P).
75. Nucci G, et al,. The sodium glucose co-transported PF04971729 provides multifaced improvement in diabetic patients inadequately controlled on metformin. Diabetologia 2011; 54 (Suppl. 1): S347. (Abstract 850).
76. th Scientific Session of American Diabetes Association 2008 June 6-8; San Francisco, CA. (Abstract 334-OR). Available from: http://professional.diabetes.org/Abstracts-Display.aspx?TYP= 1&CID=68615 (last accessed on: February 7, 2012).