Sodium glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes mellitus

Osteopathic Family Physician

Volumn 7, Issue 5, 2015, Pages 10-30

  Miller, Eden ^a   Shubrook, Jay H ^b  

^a Diabetes Nation LLC   (United States)

^b TOURO UNIVERSITY CALIFORNIA   (United States)

Author keywords

Efficacy; Renal glucose reabsorption; Safety; SGLT2 inhibitors; Type 2 diabetes mellitus

Indexed keywords

CANAGLIFLOZIN; DAPAGLIFLOZIN; EMPAGLIFLOZIN; GLIMEPIRIDE; GLIPIZIDE; GLUCOSE; METFORMIN; PIOGLITAZONE; PLACEBO; SITAGLIPTIN; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SULFONYLUREA;

ADD ON THERAPY; BODY WEIGHT CHANGE; DEHYDRATION; DOSE KIDNEY FUNCTION RELATION; DRUG APPROVAL; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG WITHDRAWAL; ESTIMATED GLOMERULAR FILTRATION RATE; FOOD AND DRUG ADMINISTRATION; FUNGAL GENITAL INFECTION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLYCEMIC CONTROL; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; HYPOTENSION; HYPOVOLEMIA; KIDNEY FAILURE; KIDNEY FUNCTION; LOW DRUG DOSE; NON INSULIN DEPENDENT DIABETES MELLITUS; ORTHOSTATIC HYPOTENSION; OSMOTIC DIURESIS; POSITIONAL DIZZINESS; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; TREATMENT DURATION; URINARY FREQUENCY; URINARY TRACT INFECTION; URINE VOLUME;

EID: 85019297749     PISSN: 1877573X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (72)

1. U.S. Department of Health and Human Services. Food and Drug Administration. FDA News Release. FDA approves Invokana to treat type 2 diabetes: First in a new class of diabetes drugs. March 29, 2013. Available from: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm345848.htm [Accessed January 7, 2015].
2. U.S. Department of Health and Human Services. Food and Drug Administration. FDA News Release. FDA approves Farxiga to treat type 2 diabetes. January 8, 2014. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm380829.htm [Accessed January 7, 2015].
3. U.S. Department of Health and Human Services. Food and Drug Administration. FDA News Release. FDA approves Jardiance to treat type 2 diabetes. August 1, 2014. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm407637.htm [Accessed January 7, 2015].
4. Garber AJ, Abrahamson MJ, Barzilay JI, et al. American Association of Clinical Endocrinologists’ comprehensive diabetes management algorithm 2013 consensus statement—executive summary. Endocr Pract 2013;19(3):536-557.
5. American Diabetes Association. Standards of Medical Care in Diabetes. Position statement: 7. Approaches to glycemic treatment. Diabetes Care 2015;38(Suppl 1):S41-S48.
6. Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med 2010;27(2):136-142.
7. Ganong WF. Section VIII. Formation & Excretion of Urine. Chapter 38: Renal Function & Micturition. In: Review of Medical Physiology, 22nd edition. New York, NY: The McGraw-Hill Companies; 2005; pp. 699-728.
8. Wilding JP. The role of the kidneys in glucose homeostasis in type 2 diabetes: clinical implications and therapeutic significance through sodium glucose co-transporter 2 inhibitors. Metabolism 2014;63(10):1228-1237.
9. 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(1):101-109.
10. DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab 2012;14(1):5-14.
11. DeFronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009;58(4):773-795.
12. Whaley JM, Tirmenstein M, Reilly TP, et al. Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus. Diabetes Metab Syndr Obes 2012;5:135-148.
13. Nomura S, Sakamaki S, Hongu M, 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 2010;53(17):6355-6360.
14. 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(1):83-90.
15. Xu J, Lee SP, Shen Qi J, et al. In vitro characterization of the selective sodium glucose co-transporter 2 inhibitor canagliflozin [abstract 239- OR]. Diabetes 2013;62(Suppl):A61.
16. 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(2):e30555.
17. Invokana® (canagliflozin). Prescribing information, revised May 2014.
18. Sha S, Devineni D, Ghosh A, et al. Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with type 2 diabetes. PLoS One 2014;9(8):e105638.
19. 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(6):601-610.
20. Devineni D, Morrow L, Hompesch M, 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(6):539-545.
21. Farxiga™ (dapagliflozin). Prescribing information, revised August 2014.
22. Jardiance® (empagliflozin). Prescribing information, revised August 2014.
23. Polidori D, Sha S, Mudaliar S, et al. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care 2013;36(8):2154-2161.
24. Sha S, Polidori D, Farrell K, et al. Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double-blind, crossover study. Diabetes Obes Metab 2015;17(2):188-197.
25. Stein P, Berg JK, Morrow L, et al. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial. Metabolism 2014;63(10):1296-1303.
26. Matthews D, Zinman B, Tong C, Meininger G, Polidori D. Glycemic efficacy of canagliflozin (CANA) is largely independent of baseline beta-cell function or insulin sensitivity [abstract 1096-P]. Diabetes 2014;63(Suppl 1):A285.
27. Perkins BA, Cherney DZ, 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(5):1480-1483.
28. Cherney DZ, Perkins BA, Soleymanlou N, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 2014;129(5):587-597.
29. Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest 2014;124(2):509-514.
30. Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebocontrolled, phase 3 trial. Diabetes Care 2010;33(10):2217-2224.
31. 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(4):262-274.
32. Rosenwasser RF, Sultan S, Sutton D, Choksi R, Epstein BJ. SGLT-2 inhibitors and their potential in the treatment of diabetes. Diabetes Metab Syndr Obes 2013;6:453-467.
33. Bhatia J, Gamad N, Bharti S, Arya DS. Canagliflozin-current status in the treatment of type 2 diabetes mellitus with focus on clinical trial data. World J Diabetes 2014;5(3):399-406.
34. Nauck MA. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther 2014;8:1335-1380.
35. 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(4):372-382.
36. Wilding JP, Charpentier G, Hollander P, et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial. Int J Clin Pract 2013;67(12):1267-1282.
37. Roden M, Weng J, Eilbracht J, et al. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol 2013;1(3):208-219.
38. 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(9896):941-950.
39. Leiter LA, Yoon KH, Arias P, et al. Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: a randomized, double-blind, phase 3 study. Diabetes Care 2014;38(3):355-364.
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(12):2582-2592.
41. Schernthaner G, Gross JL, Rosenstock J, et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52- week randomized trial. Diabetes Care 2013;36(9):2508-2515.
42. 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(5):467-477.
43. Bode B, Stenlöf K, Sullivan D, Fung A, Usiskin K. Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: a randomized trial. Hosp Pract (1995) 2013;41(2):72-84.
44. Yale JF, Bakris G, Cariou B, et al. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab 2013;15(5):463-473.
45. Sha S, Polidori D, Heise T, et al. Effect of the sodium glucose cotransporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus. Diabetes Obes Metab 2014;16(11):1087-1095.
46. Usiskin K, Kline I, Fung A, Mayer C, Meininger G. Safety and tolerability of canagliflozin in patients with type 2 diabetes mellitus: pooled analysis of phase 3 study results. Postgrad Med 2014;126(3):16-34.
47. Sinclair A, Bode B, Harris S, et al. Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. BMC Endocr Disord 2014;14:37.
48. Yamout H, Perkovic V, Davies M, et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes and stage 3 nephropathy. Am J Nephrol 2014;40(1):64-74.
49. Bailey CJ, Morales Villegas EC, Woo V, Tang W, Ptaszynska A, List JF. Efficacy and safety of dapagliflozin monotherapy in people with type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial. Diabet Med 2014;32(4):531-534.
50. Bailey CJ, Gross JL, Hennicken D, Iqbal N, Mansfield TA, List JF. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebocontrolled 102-week trial. BMC Med 2013;11:43.
51. 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(9):2015-2022.
52. Strojek K, Yoon KH, Hruba V, Elze M, Langkilde A, Parikh S. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, doubleblind, placebo-controlled trial. Diabetes Obes Metab 2011;13(10):928-938.
53. Rosenstock J, Vico M, Wei L, Salsali A, List JF. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care 2012;35(7):1473-1478.
54. Wilding JP, Woo V, Soler NG, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med 2012;156(6):405-415.
55. Matthaei S, Rohwedder K, Grohl A, Johnsson E. Dapagliflozin improves glycaemic control and reduces body weight as add-on therapy to metformin plus sulphonylurea [abstract 937]. Diabetologia 2013;56(Suppl):S374.
56. Kohan DE, Fioretto PO, Tang W, List JF. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int 2014;85(4):962-971.
57. 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(3):1020-1031.
58. Basile J, Ptaszynska A, Ying L, Sugg J, Parikh S. The effects of dapagliflozin on cardiovascular risk factors in patients with type 2 diabetes mellitus [abstract]. Circ Cardiovasc Qual Outcomes 2012;5(Suppl):A59.
59. Ptaszynska A, Johnsson KM, Parikh SK, de Bruin TW, Apanovitch AM, List JF. Safety profile of dapagliflozin for type 2 diabetes: pooled analysis of clinical studies for overall safety and rare events. Drug Saf 2014;37(10):815-829.
60. Johnsson KM, Ptaszynska A, Schmitz B, Sugg J, Parikh SJ, List JF. Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J Diabetes Complications 2013;27(5):479-484.
61. Johnsson KM, Ptaszynska A, Schmitz B, Sugg J, Parikh SJ, List JF. Urinary tract infections in patients with diabetes treated with dapagliflozin. J Diabetes Complications 2013;27(5):473-478.
62. European Medicines Agency. Forxiga (dapagliflozin): Assessment Report. Procedure no. EMEA/H/C/002322. 2012. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002322/WC500136024.pdf [Accessed January 7, 2015].
63. Wilding JP, Norwood P, T’joen C, Bastien A, List JF, Fiedorek FT. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulinindependent treatment. Diabetes Care 2009;32(9):1656-1662.
64. Anderson SL. Dapagliflozin efficacy and safety: a perspective review. Ther Adv Drug Saf 2014;5(6):242-254.
65. Häring HU, Merker L, Seewaldt-Becker E, et al. Empagliflozin as an addon to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 2013;36(11):3396-3404.
66. Häring HU, Merker L, Seewaldt-Becker E, et al. Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 2014;37(6):1650-1659.
67. Ridderstråle M, Andersen KR, Zeller C, et al. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, doubleblind, phase 3 trial. Lancet Diabetes Endocrinol 2014;2(9):691-700.
68. Kovacs CS, Seshiah V, Swallow R, et al. Empagliflozin improved 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 2013;16(2):147-158.
69. Rosenstock J, Jelaska A, Frappin G, et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care 2014;37(7):1815-1823.
70. Barnett AH, Mithal A, Manassie J, et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2014;2(5):369-384.
71. Toto RD, Wanner C, Gerich J, et al. No overall increase in volume depletion events with empagliflozin (EMPA) in a pooled analysis of more than 11,000 patients with type 2 diabetes (T2DM). J Am Soc Nephrol 2013;24(Suppl):Abstract SA-PO373
72. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012;35(6):1364-1379.