Sodium-glucose linked transporter 2 (SGLT2) inhibitors in the management of type-2 diabetes: A drug class overview

P and T

Volumn 40, Issue 7, 2015, Pages 451-462

  Mosley, Juan F ^a   Smith, Lillian ^a   Everton, Emily ^b   Fellner, Chris ^b  

^a FLORIDA A AND M UNIVERSITY   (United States)

^b MediMedia Managed Markets   (United States)

Author keywords

Canagliflozin; Dapagliflozin; Empagliflozin; Sodium glucose linked transporter 2 (SGLT2) inhibitors; Type 2 diabetes mellitus (T2DM)

Indexed keywords

CANAGLIFLOZIN; DAPAGLIFLOZIN PLUS METFORMIN; EMPAGLIFLOZIN PLUS LINAGLIPTIN; PIOGLITAZONE; SITAGLIPTIN; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SULFONYLUREA;

GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE TRANSPORT; GLUCOSE URINE LEVEL; GLUCOSURIA; HUMAN; HYPOGLYCEMIA; NON INSULIN DEPENDENT DIABETES MELLITUS; NOTE; WEIGHT REDUCTION;

EID: 84937208890     PISSN: 10521372     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Note

References (67)

1. American Diabetes Association: Standards of medical care in diabetes—2014. Diabetes Care 2014;37(suppl 1):S14–S80.
2. Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014. Atlanta, Georgia: U.S. Department of Health and Human Services; 2014.
3. Cheung BM, Ong KL, Cherny SS, et al. Diabetes prevalence and therapeutic target achievement in the United States, 1999 to 2006. Am J Med 2009;122:443–453.
4. Garber AL, Abrahamson MJ, Barzilay JI, et al. American Association of Clinical Endocrinologists’ comprehensive diabetes management algorithm 2013 consensus statement. Endocr Pract 2013;19(suppl 2):1–48.
5. Valentine V. The role of the kidney and sodium-glucose cotransporter-2 inhibition in diabetes management. Clin Diabetes 2012;30:151–155.
6. List JF, Whaley JM. Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney Int 2011;79(suppl 120):S20–S27.
7. Rizza RA, Gerich JE, Haymond MW, et al. Control of blood sugar in insulin-dependent diabetes: comparison of an artificial endocrine pancreas, continuous subcutaneous insulin infusion, and intensified conventional insulin therapy. N Engl J Med 1980;303:1313–1318.
8. Gerich JE. Physiology of glucose homeostasis. Diabetes Obes Metab 2000;2:345–350.
9. Wahren J, Felig P, Hagenfeldt L. Physical exercise and fuel homeostasis in diabetes mellitus. Diabetologia 1978;14:213–222.
10. Consoli A, Kennedy F, Miles J, et al. Determination of Krebs cycle metabolic carbon exchange in vivo and its use to estimate the individual contributions of gluconeogenesis and glycogenolysis to overall glucose output in man. J Clin Invest 1987;80:1303–1310.
11. Chao EC, Henry RR. SGLT2 inhibition: a novel strategy for diabetes treatment. Nat Rev Drug Discov 2010;9:551–559.
12. 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.
13. Bays H. Sodium glucose co-transporter type 2 (SGLT2) inhibitors: targeting the kidney to improve glycemic control in diabetes mellitus. Diabetes Ther 2013;4:195–220.
14. Farber SJ, Berger EY, Earle DP. Effect of diabetes and insulin on the maximum capacity of the renal tubules to reabsorb glucose. J Clin Invest 1951;30:125–129.
15. Mogensen CE. Maximum tubular reabsorption capacity for glucose and renal hemodynamics during rapid hypertonic glucose infusion in normal and diabetic subjects. Scand J Clin Lab Invest 1971;28:101–109.
16. 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.
17. Johnson & Johnson. U.S. FDA approves Invokana (canagliflozin) for the treatment of adults with type 2 diabetes. March 29, 2013. Available at: http://www.jnj.com/news/all/us-fda-approves-invokana-canagliflozin-for-the-treatment-of-adults-with-type-2-diabetes. Accessed April 16, 2015.
18. Food and Drug Administration. FDA approves Farxiga to treat type 2 diabetes. January 8, 2014. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm380829.htm. Accessed April 16, 2015.
19. Food and Drug Administration. FDA approves Jardiance to treat type 2 diabetes. August 1, 2014. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm407637.htm. Accessed April 16, 2015.
20. Johnson & Johnson. U.S. FDA approves Invokamet (canagliflozin/metformin HCl) for the treatment of adults with type 2 diabetes. August 8, 2014. Available at: https://www.jnj.com/news/all/US-FDA-Approves-INVOKAMET-canagliflozin-metformin-HClfor-the-Treatment-of-Adults-with-Type-2-Diabetes. Accessed April 16, 2015.
21. AstraZeneca. US FDA approves once-daily Xigduo XR tablets for adults with type 2 diabetes. October 30, 2014. Available at: http://www.astrazeneca.com/Media/Press-releases/Article/20141030-us-fda-approve-oncedaily-xigduo-xr. Accessed April 16, 2015.
22. Boehringer Ingelheim. U.S. FDA approves first-in-class Glyxambi (empagliflozin/linagliptin) tablets for adults with type 2 diabetes. February 2, 2015. Available at: http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2015/2-2-2015-us-fda-approves-first-in-class-glyxambi-empagliflozin-linagliptin-tablets-adults-type-2-diabetes.html. Accessed April 16, 2015.
23. 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.
24. 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.
25. Liu JJ, Lee T, DeFronzo RA. Why do SGLT2 inhibitors inhibit only 30–50% of renal glucose reabsorption in humans? Diabetes 2012;61:2199–2204.
26. Kitabchi A, Umpierrez G, Miles J, et al. Hyperglycemic crisis in adult patients with diabetes. Diabetes Care 2009;32:1335–1343.
27. Henry RR, Rosenstock J, Edelman S, et al. Exploring the potential of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a randomized, double-blind, placebo-controlled pilot study. Diabetes Care 2015;38:412–419.
28. Perkins B, Cherney D, Partridge H, et al. Sodium-glucose cotransporter 2 inhibition and glycemic control in type 1 diabetes: results of an 8-week open-label proof-of-concept trial. Diabetes Care 2014;37:1480–1483.
29. Bays H, Weinstein R, Law G, et al. Canagliflozin: effects in overweight and obese subjects without diabetes mellitus. Obesity (Silver Springs) 2014;22:1042–1049.
30. Bolinder J, Ljunggren Ö, Kullberg J, et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 2012;97:1020–1031.
31. Mayo Clinic. Counting calories: getting back to weight loss basics. April 22, 2015. Available at: http://www.mayoclinic.org/healthyliving/weight-loss/in-depth/calories/art-20048065. Accessed April 28, 2015.
32. McCrimmon RJ, Evans ML, Jacob RJ, et al. AICAR and phlorizin reverse the hypoglycemia-specific defect in glucagon secretion in the diabetic BB rat. Am J Physiol Endocrinol Metab 2002;283:E1076–E1083.
33. 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.
34. 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.
35. Invokana (canagliflozin) prescribing information. Titusville, New Jersey: Janssen Pharmaceuticals, Inc.; March 2015. Available at: http://www.invokana.com/prescribing-information.pdf. Accessed April 15, 2015.
36. 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.
37. University of Tennessee Stats Design and Analysis Web Guide. Least squares means. February 2014. Available at: http://dawg.utk.edu/glossary/g_least_squares_means.htm. Accessed January 26, 2015.
38. Forst T, Guthrie R, Goldenberg R, et al. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone. Diabetes Obes Metab 2014;16:467–477.
39. Schernthaner G, Gross J, Rosenstock J, et al. Canagloflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea. Diabetes Care 2013;36:2508–2515.
40. Cefalu W, Leiter L, 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 randomized, double-blind, phase 3 non-inferiority trial. Lancet 2013;382:941–950.
41. ClinicalTrials.gov. The CANTATA-D (Canagliflozin Treatment and Trial Analysis)––DPP-4 Inhibitor Comparator Trial. NCT01106677. July 25, 2013. Available at: https://clinicaltrials.gov/ct2/show/NCT01106677?term=nct01106677&rank=1. Accessed April 16, 2015.
42. ClinicalTrials.gov. The CANTATA-MSU Trial (Canagliflozin Treatment and Trial Analysis––Metformin and Sulfonylureas). NCT01106625. June 12, 2013. Available at: https://clinicaltrials.gov/ct2/show/NCT01106625. Accessed April 17, 2015.
43. Farxiga (dapagliflozin) prescribing information. Wilmington, Delaware: AstraZeneca; March 2015. Available at: http://www.azpicentral.com/farxiga/pi_farxiga.pdf#page=1. Accessed April 15, 2015.
44. Ji L, Ma J, Li H, et al. Dapagliflozin as monotherapy in drug-naïve Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III study. Clin Ther 2014;36:84–100.
45. Bailey C, Gross J, Pieters A, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomized, double-blind, placebo-controlled trial. Lancet 2010;375:2223–2233.
46. Nauck M, Del Prato S, Meier J, et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin. Diabetes Care 2011;34:2015–2022.
47. Jardiance (empagliflozin) prescribing information. Ridgefield, Connecticut: Boehringer Ingelheim Pharmaceuticals, Inc.; August 2014. Available at: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Jardiance/jardiance.pdf. Accessed April 15, 2015.
48. Ferrannini E, Seman L, Seewaldt-Becker E, et al. A phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes. Diabetes Obes Metab 2013;15:721–728.
49. ClinicalTrials.gov. Efficacy and safety of empagliflozin (BI 10773) versus placebo and sitagliptin over 24 weeks in patients with type 2 diabetes. NCT01177813. May 16, 2014. Available at: https://clinicaltrials.gov/ct2/show/results/NCT01177813?term=empagliflozin&rank=19§=X4301256#othr. Accessed April 21, 2015.
50. Häring HU, Merker L, Seewaldt-Becker E, et al. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes. Diabetes Care 2013;36:3396–3404.
51. Kovacs CS, Seshiah V, Swallow R, et al. Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab 2014;16:147–158.
52. Devineni D, Curtin CR, Polidori D, et al. Pharmacokinetics and pharmacodynamics of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in subjects with type 2 diabetes mellitus. J Clin Pharmacol 2013;53:601–610.
53. Kasichayanula S, Liu X, Zhang W, et al. Effect of a high-fat meal on the pharmacokinetics of dapagliflozin, a selective SGLT2 inhibitor, in healthy subjects. Diabetes Obes Metab 2011;13:770–773.
54. Riggs M, Stabb A, Seman L, et al. Population pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with type 2 diabetes. J Clin Pharmacol 2013;53:1028–1038.
55. Wilding J, Woo V, Soler N, 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.
56. Wooltorton E. Rosiglitazone (Avandia) and pioglitazone (Actos) and heart failure. CMAJ 2002;166:219.
57. Neal B, Perkovic V, de Zeeuw D, et al. Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS): a randomized placebo-controlled trial. Am Heart J 2013;166:217–223.
58. Neal B, Perkovic V, de Zeeuw D, et al. Efficacy and safety of canagliflozin, an inhibitor of sodium glucose cotransporter 2, when used in conjunction with insulin therapy in patients with type 2 diabetes. Diabetes Care 2015;38:403–411. doi: 10.2337/dc14-1237.
59. Food and Drug Administration. FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. May 15, 2015. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm. Accessed June 4, 2015.
60. ClinicalTrials.gov. PK study of dapagliflozin in pediatric subjects with T2DM. NCT01525238. February 6, 2015. Available at: https://clinicaltrials.gov/ct2/show/NCT01525238. Accessed April 28, 2015.
61. ClinicalTrials.gov. A study to evaluate the pharmacokinetics, pharmacodynamics, and safety of canagliflozin in older children and adolescents with type 2 diabetes mellitus. NCT02000700. April 17, 2015. Available at: https://clinicaltrials.gov/ct2/show/NCT02000700?term=canagliflozin&rank=1. Accessed April 28, 2015.
62. Bode B, Stenlöf K, Harris S, et al. Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55–80 years with type 2 diabetes. Diabetes Obes Metab 2015;17:294–303.
63. Devineni D, Curtin CR, Marbury TC, et al. Effect of hepatic or renal impairment on the pharmacokinetics of canagliflozin, a sodiumglucose cotransporter 2 inhibitor. Clin Ther 2015;37:610–628.
64. Sarashina A, Ueki K, Sasaki T, et al. Effects of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus. Clin Ther 2014;36:1606–1615.
65. Macha S, Rose P, Mattheus M, et al. Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with hepatic impairment. Diabetes Obes Metab 2014;16:118–123.
66. Canagliflozin. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, Colorado. Available at: http://www.micromedexsolutions.com. Accessed January 28, 2015.
67. Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med 2010; 363:1410–1418.