Renal sodium glucose cotransporter 2 inhibitors as a novel therapeutic approach to treatment of type 2 diabetes: Clinical data and mechanism of action

Journal of Diabetes Investigation

Volumn 5, Issue 3, 2014, Pages 265-275

  Fujita, Yoshihito ^a   Inagaki, Nobuya ^a  

^a KYOTO UNIVERSITY   (Japan)

Author keywords

Novel antidiabetic agents; Renal glucose reabsorption; Sodium glucose cotransporter 2 inhibitors

Indexed keywords

ADIPONECTIN; CANAGLIFLOZIN; DAPAGLIFLOZIN; EMPAGLIFLOZIN; GLIMEPIRIDE; GLIPIZIDE; HEMOGLOBIN A1C; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; IPRAGLIFLOZIN; LUSEOGLIFLOZIN; METFORMIN; ORAL ANTIDIABETIC AGENT; SITAGLIPTIN; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SULFONYLUREA; TOFOGLIFLOZIN; TRIACYLGLYCEROL;

ANTIDIABETIC ACTIVITY; ARTICLE; BLADDER CANCER; BREAST CANCER; CEREBROVASCULAR ACCIDENT; DRUG EFFECT; DRUG EFFICACY; DRUG POTENCY; DRUG POTENTIATION; DRUG SAFETY; DRUG SELECTIVITY; DRUG TOLERABILITY; GENITAL TRACT INFECTION; GLUCOSE BLOOD LEVEL; GLUCOTOXICITY; GLYCEMIC CONTROL; HEART INFARCTION; HOMEOSTASIS MODEL ASSESSMENT OF INSULIN RESISTANCE; HUMAN; HYPOGLYCEMIA; INSULIN RESISTANCE; INTRAABDOMINAL FAT; KIDNEY FAILURE; LIPID BLOOD LEVEL; METABOLIC PARAMETERS; MONOTHERAPY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SUBCUTANEOUS FAT; SYSTOLIC BLOOD PRESSURE; UNSTABLE ANGINA PECTORIS; URINARY TRACT INFECTION; WEIGHT REDUCTION;

EID: 84899904943     PISSN: 20401116     EISSN: 20401124     Source Type: Journal    
DOI: 10.1111/jdi.12214     Document Type: Article

References (85)

1. International Diabetes Federation. IDF Diabetes Atlas, 6th edn. International Brussels, Brussels, Belgium, Belgium, International Diabetes Federation, 2013.
2. Danaei G, Finucane MM, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 2011; 378: 31-40.
3. Prentki M, Nolan CJ. Islet cell failure in type 2 diabetes. J Clin Invest 2006; 116: 1802-1812.
4. O'Rahilly S. Human obesity and insulin resistance: lessons from experiments of nature. Biochem Soc Trans 2007; 35: 33-36.
5. Pirola L, Balcerczyk A, Okabe J, et al. Epigenetic phenomena linked to diabetic complications. Nat Rev Endocrinol 2010; 6: 665-675.
6. L'Abbate A. Large and micro coronary vascular involvement in diabetes. Pharmacol Rep 2005; 57(Suppl.): 3-9.
7. UKPDS 34. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352: 854-865.
8. UKPDS 33. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352: 837-853.
9. Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995; 28: 103-117.
10. Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359: 1577-1589.
11. American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care 2014; 37(Suppl 1): S14-S80.
12. Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin or glyburide monotherapy. N Engl J Med 2007; 356: 1387-1388.
13. Ong KL, Cheung BM, Wong LY, et al. Prevalence, treatment, and control of diagnosed diabetes in the U.S. National Health and Nutrition Examination Survey 1999-2004. Ann Epidemiol 2008; 18: 222-229.
14. Rahmoune H, Thompson PW, Ward JM, 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.
15. Bakris GL, Fonseca VA, Sharma K, et al. Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int 2009; 75: 1272-1277.
16. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 2011; 91: 733-794.
17. Abdul-Ghani MA, DeFronzo RA. Inhibition of renal glucose reabsorption: a novel strategy for achieving glucose control in type 2 diabetes. Endocr Pract 2008; 6: 782-790.
18. Ferrannini E. Learning from glycosuria. Diabetes 2011; 60: 695-696.
19. Hediger MA, Kanai Y, You G, et al. Mammalian ion-coupled solute transporters. J Physiol 1995; 482: 7S-17S.
20. Chen J, Williams S, Ho S, et al. Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members. Diabetes Ther 2010; 1: 57-92.
21. Vallon V, Platt KA, Cunard R, et al. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol 2011; 22: 104-112.
22. Wright EM, Turk E. The sodium/glucose cotransport family SLC5. Pflugers Arch 2004; 447: 510-518.
23. Wright EM. Renal Na-glucose cotransporters. Am J Renal Physiol 2001; 280: F10-F18.
24. Martín MG, Turk E, Lostao MP, et al. Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactosemalabsorption. Nat Genet 1996; 12: 216-220.
25. van den Heuvel LP, Assink K, Willemsen M, et al. Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2). Hum Genet 2002; 111: 544-547.
26. Calado J, Santer R, Rueff J. Effect of kidney disease on glucose handling (including genetic defects). Kidney Int Suppl 2011; 79: S7-S13.
27. Ehrenkranz JR, Lewis NG, Kahn CR, et al. Phlorizin: a review. Diabetes Metab Res Rev 2005; 21: 31-38.
28. Rossetti L, Smith D, Shulman GI, et al. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 1987; 79: 1510-1515.
29. FDA, FDA NEWS RELEASE. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm380829.htm-
30. Gorboulev V, Schürmann A, Vallon V, et al. Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 2012; 6: 187-196.
31. Harada N, Inagaki N. Role of sodium-glucose transporters in glucose uptake of the intestine and kidney. J Diabetes Invest 2012; 3: 352-353.
32. Abdul-Ghani MA, DeFronzo RA, Norton L. Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30-50% of filtered glucose load in humans. Diabetes 2013; 10: 3324-3328.
33. Zambrowicz B, Freiman J, Brown PM, et al. LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther 2012; 92: 158-169.
34. Fukushima M, Suzuki H, Seino Y. Insulin secretion capacity in the development from normal glucose tolerance to type 2 diabetes. Diabetes Res Clin Pract 2004; 66(Suppl 1): S37-S43.
35. Inagaki N, Kondo K, Yoshinari T, et al. Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, 12-week study. Diabetes Obes Metab 2013; 15: 1136-1145.
36. Zhang L, Feng Y, List J, et al. Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight. Diabetes Obes Metab 2010; 12: 510-516.
37. Clar C, Gill JA, Court R, et al. Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. BMJ Open 2012; 2: 1-12.
38. Dietrich E, Powell J, Taylor JR. Canagliflozin: a novel treatment option for type 2 diabetes. Drug Des Devel Ther 2013; 22: 1399-1408.
39. Stenlöf K, Cefalu WT, Kim KA, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab 2013; 15: 372-382.
40. Lavalle-González FJ, Januszewicz A, Davidson J, et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia 2013; 56: 2582-2592.
41. Cefalu WT, Leiter LA, Yoon KH, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 2013; 382: 941-950.
42. Cefalu WT, Leiter LA, Yoon KH, et al. Canagliflozin demonstrates durable glycemic improvements over 104 weeks versus glimepiride in subjects with type 2 diabetes mellitus on metformin. Diabetes 2013; 62(Suppl 1A): LB18.
43. Bailey CJ, Gross JL, Pieters A, 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.
44. Strojek K, Yoon KH, Hruba V, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab 2011; 13: 928-938.
45. Rosenstock J, Vico M, Wei L, et al. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA1c, body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care 2012; 35: 1473-1478.
46. Wilding JPH, Woo V, Soler NG, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin. Ann Intern Med 2012; 156: 405-415.
47. Bailey CJ, Gross JL, Hennicken D, et al. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial. BMC Med 2013; 11: 43.
48. Nauck MA, Del Prato S, Meier JJ, 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 noninferiority trial. Diabetes Care 2011; 34: 2015-2022.
49. Prato SD, et al. Durability of dapagliflozin vs. glipizide as add-on therapies in T2DM inadequately controlled on metformin: 4-year data. Diabetes 2013; 62(Suppl 1A): LB17.
50. Ferrannini E, Seman LJ, Seewaldt-Becker E, et al. The potent and highly selective sodium-glucose co-transporter (SGLT-2) inhibitor BI10773 is safe and efficacious as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2010; 53: S351.
51. Rosenstock J, Jelaska A, Wang F, et al. Empagliflozin as add-on to basal insulin for 78 weeks improves glycemic control with weight loss in insulin-treated type 2 diabetes. Diabetes 2013; 62: A285.
52. Ferrannini E, Berk A, Hantel S, et al. Long-term safety and efficacy of empagliflozin, sitagliptin, and metformin: an active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes. Diabetes Care 2013; 36: 4015-4021.
53. Goto K, Kashiwagi A, Kazuta K, et al. Ipragliflozin reduces A1C and body weight in type 2 diabetes patients who have inadequate glycemic control on metformin alone: ILLUMINATE study. Diabetes 2012; 61: A269.
54. Kawano H, Kashiwagi A, Kazuta K, et al. Long-term safety, tolerability and efficacy of ipragliflozin in Japanese patients with type 2 diabetes mellitus: IGNITE. Diabetes 2012; 61(Suppl 1): A610.
55. Seino Y, Sasaki T, Fukatsu A, et al. Luseogliflozin, a SGLT2 inhibitor, improves glycaemic control and reduces body weight as monotherapy up to 52 weeks in Japanese patients with type 2 diabetes mellitus. Diabetologia 2013; 56(Suppl 1): S384.
56. Inagaki N, Seino Y, Sasaki T, et al. Luseogliflozin, a selective SGLT2 inhibitor, added on to glimepiride for 52 weeks improves glycaemic control with no major hypoglycaemia in Japanese type 2 diabetes patients. Diabetologia 2013; 56(Suppl 1): S82.
57. Haneda M, Seino Y, Sasaki T, et al. Luseogliflozin, a SGLT2 inhibitor, as add-on therapy to 5 types of oral antidiabetic drugs improves glycaemic control and reduces body weight in Japanese patients with type 2 diabetes mellitus. Diabetologia 2013; 56(Suppl 1): S384.
58. Tanizawa Y, Araki E, Tobe K, et al. Efficacy and safety of tofogliflozin administered for 52 weeks as monotherapy or combined with other oral hypoglycaemic agents in Japanese patients with type 2 diabetes. Diabetologia 2013; 56(Suppl 1): S82-S83.
59. Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 2013; 159: 262-274.
60. Riser TaylorS, Harris KB. The clinical efficacy and safety of sodium glucose cotransporter-2 inhibitors in adults with type 2 diabetes mellitus. Pharmacotherapy 2013; 33: 984-999.
61. Food and Drug Administration. FDA Briefing Document NDA 202293. Dapagliflozin 5 and 10 mg. 2011. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM262994.pdf.
62. Burki TK. FDA rejects novel diabetes drug over safety fears. Lancet 2012; 379: 507.
63. Cefalu WT, Leiter LA, Debruin TW, et al. Dapagliflozin treatment for type 2 diabetes mellitus patients with comorbid cardiovascular disease and hypertension. Diabetes 2012; 61(Suppl 1): A271.
64. Leiter LA, Cefalu WT, Debruin TW, et al. Efficacy and safety of dapagliflozin for type 2 diabetes mellitus patients with a history of cardiovascular disease. Diabetes 2012; 61(Suppl 1): A287.
65. European Medicines Agency. Assessment Report: Forxiga (Dapagliflozin). Procedure no. EMEA/H/C/002322. London: European Medicines Agency; 2012. Accessed at www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002322/WC500136024.pdf.
66. Matthews DR, Fulcher G, Perkovic V, et al. Efficacy and safety of canagliflozin (CANA), an inhibitor of sodium glucose co-transporter 2 (SGLT2), added-on to insulin therapy +/- oral agents in type 2 diabetes. Diabetologia 2012; 55(Suppl 1): S314-S315.
67. Han S, Hagan DL, Taylor JR, et al. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes 2008; 57: 1723-1729.
68. Oku A, Ueta K, Arakawa K, et al. T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes 1999; 48: 1794-1800.
69. Oku A, Ueta K, Arakawa K, et al. Correction of hyperglycemia and insulin sensitivity by T-1095, an inhibitor of renal Na+-glucose cotransporters, in streptozotocin-induced diabetic rats. Jpn J Pharmacol 2000; 84: 351-354.
70. Luippold G, Klein T, Mark M, et al. Empagliflozin, a novel potent and selective SGLT-2 inhibitor, improves glycaemic control alone and in combination with insulin in streptozotocin-induced diabetic rats, a model of type 1 diabetes mellitus. Diabetes Obes Metab 2012; 14: 601-607.
71. Suzuki M, Honda K, Fukazawa M, et al. Tofogliflozin, a potent and highly specific sodium/glucose cotransporter 2 inhibitor, improves glycemic control in diabetic rats and mice. J Pharmacol Exp Ther 2012; 341: 692-701.
72. Arakawa K, Ishihara T, Oku A, et al. Improved diabetic syndrome in C57BL/KsJ-db/db mice by oral administration of the Na+-glucose cotransporter inhibitor T-1095. Br J Pharmacol 2001; 132: 578-586.
73. Liang Y, Arakawa K, Ueta K, et al. Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models. PLoS ONE 2012; 7: e30555.
74. Nicolle LE, Capuano G, Ways K, et al. Effect of canagliflozin, a sodium-glucose cotransporter 2(SGLT2) inhibitors, on bacteria and urinary tract infection in subjects with type 2 diabetes enrolled in a 12-week, phase 2 study. Curr Med Res Opin 2012; 28: 1167-1171.
75. Kim Y, Babu AR. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes 2012; 5: 313-327.
76. Tahrani AA, Bailey CJ, Del Prato S, et al. Management of type 2 diabetes: new and future developments in treatment. Lancet 2011; 378: 182-197.
77. Tahara A, Kurosaki E, Yokono M, et al. Pharmacological profile of ipragliflozin (ASP1941), a novel selective SGLT2 inhibitor, in vitro and in vivo. Naunyn Schmiedebergs Arch Pharmacol 2012; 385: 423-436.
78. Grempler R, Thomas L, Eckhardt M, et al. Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab 2012; 14: 83-90.
79. Ohtake Y, Sato T, Kobayashi T, et al. Discovery of tofogliflozin, a novel C-Arylglucoside with an O-spiroketal ring system, as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem 2012; 55: 7828-7840.
80. Kakinuma H, Oi T, Hashimoto-Tsuchiya Y, et al. (1S)-1, 5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-d-glucito l (TS-071) is a potent, selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes treatment. J Med Chem 2010; 53: 3247-3261.
81. 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; 139: 51-59.
82. Ferrannini E, Ramos SJ, Salsali A, et al. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise. Diabetes Care 2010; 33: 2217-2224.
83. Roden M, Weng J, Eilbracht J, et al. Empagliflozin monotherapy improves glucose control in drug-naïve patients with type 2 diabetes. Diabetes 2013; 62(Suppl 1): A280.
84. Kashiwagi A, Takinami Y, Kazuta K, et al. Efficacy of Ipragliflozin, a new SGLT2 inhibitor, in the treatment of type 2 diabetes. J Jpn Diabetes Soc 2012; 55(Suppl 1): S-276 (Japanese).
85. Araki E, Kaku K, Watada H, et al. Verification of the efficacy and safety of tofogliflozin, a novel SGLT2 inhibitor, in Japanese patients with type 2 diabetes mellitus: results from a phase 2/3 clinical study. Diabetologia 2013; 56(Suppl 1): S371.