Sodium-glucose co-transporter 2 inhibitors for type 2 diabetes mellitus: An overview for the primary care physician

International Journal of Clinical Practice

Volumn 71, Issue 5, 2017, Pages

  Dandona, Paresh ^a   Chaudhuri, Ajay ^a  

^a UNIVERSITY AT BUFFALO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CANAGLIFLOZIN; DAPAGLIFLOZIN; EMPAGLIFLOZIN; HEMOGLOBIN A1C; INSULIN; METFORMIN; PLACEBO; SODIUM GLUCOSE COTRANSPORTER 2; SULFONYLUREA; 2-(3-(4-ETHOXYBENZYL)-4-CHLOROPHENYL)-6-HYDROXYMETHYLTETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; ANTIDIABETIC AGENT; BENZHYDRYL DERIVATIVE; GLUCOSIDE;

ANTIDIABETIC ACTIVITY; BLADDER CANCER; BLOOD PRESSURE; BREAST CANCER; CARDIOVASCULAR DISEASE; CARDIOVASCULAR MORTALITY; CLINICAL PRACTICE; DRUG EFFICACY; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; FRACTURE; FUNGAL GENITAL INFECTION; GENERAL PRACTITIONER; GENITAL TRACT INFECTION; GLUCOSE TRANSPORT; GLYCEMIC CONTROL; HUMAN; HYPERKALEMIA; HYPOGLYCEMIA; HYPOTENSION; HYPOVOLEMIA; KIDNEY TUBULE ABSORPTION; NON INSULIN DEPENDENT DIABETES MELLITUS; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK REDUCTION; SIDE EFFECT; URINARY TRACT INFECTION; WEIGHT REDUCTION; ANTAGONISTS AND INHIBITORS; PRIMARY HEALTH CARE; TREATMENT OUTCOME;

BENZHYDRYL COMPOUNDS; CANAGLIFLOZIN; DIABETES MELLITUS, TYPE 2; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; PRIMARY HEALTH CARE; SODIUM-GLUCOSE TRANSPORTER 2; TREATMENT OUTCOME;

EID: 85018663946     PISSN: 13685031     EISSN: 17421241     Source Type: Journal    
DOI: 10.1111/ijcp.12937     Document Type: Review

References (112)

1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128.
2. Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med. 1993;329:304-309.
3. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986.
4. 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.
5. UK Prospective Diabetes Study UKPDS Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-853.
6. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854-865.
7. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405-412.
8. Stark Casagrande S, Fradkin JE, Saydah SH, et al. The prevalence of meeting A1C, blood pressure, and LDL goals among people with diabetes, 1988-2010. Diabetes Care 2013; 36: 2271-2279.
9. Khan H, Lasker SS, Chowdhury TA. Exploring reasons for very poor glycaemic control in patients with type 2 diabetes. Prim Care Diabetes. 2011;5:251-255.
10. Fox KM, Gerber RA, Bolinder B, et al. Prevalence of inadequate glycemic control among patients with type 2 diabetes in the United Kingdom general practice research database: a series of retrospective analyses of data from 1998 through 2002. Clin Ther. 2006;28:388-395.
11. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2016 executive summary. Endocr Pract. 2016;22:84-113.
12. International Diabetes Federation IDF Diabetes, 7 ed. Brussels: International Diabetes Federation, 2015. http://www.diabetesatlas.org. Accessed May 13, 2016.
13. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013;36:S67-S74.
14. Bays H. From victim to ally: the kidney as an emerging target for the treatment of diabetes mellitus. Curr Med Res Opin. 2009;25:671-681.
15. Hirsch IB, Molitch ME. Clinical decisions. Glycemic management in a patient with type 2 diabetes. N Engl J Med. 2013;369:1370-1372.
16. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011;91:733-794.
17. Hediger MA, Rhoads DB. Molecular physiology of sodium-glucose cotransporters. Physiol Rev. 1994;74:993-1026.
18. Thorens B, Mueckler M. Glucose transporters in the 21st century. Am J Physiol Endocrinol Metab. 2010;298:E141-E145.
19. Dominguez JH, Camp K, Maianu L, Garvey WT. Glucose transporters of rat proximal tubule: differential expression and subcellular distribution. Am J Physiol. 1992;262:F807-F812.
20. Zelikovic I. Aminoaciduria and glycosuria. In: Avner ED, Harmon WE, Niaudet P, eds. Pediatric Nephrology, 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:701-728.
21. Moe OW, Wright SH, Palacín M. Renal handling of organic solutes. In: Brenner BM, Rector FC, ed. Brenner and Rector's the Kidney. Philadelphia, PA: Saunders Elsevier; 2008:214-247.
22. Mogensen CE. Maximum tubular reabsorption capacity for glucose and renal hemodynamcis during rapid hypertonic glucose infusion in normal and diabetic subjects. Scand J Clin Lab Invest. 1971;28:101-109.
23. 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.
24. Vestri S, Okamoto MM, de Freitas HS, et al. Changes in sodium or glucose filtration rate modulate expression of glucose transporters in renal proximal tubular cells of rat. J Membr Biol. 2001;182:105-112.
25. Abdul-Ghani MA, Norton L, Defronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocrine Rev. 2011;32:515-531.
26. Wright EM, Turk E, Martin MG. Molecular basis for glucose-galactose malabsorption. Cell Biochem Biophys. 2002;36:115-121.
27. Zambrowicz B, Ogbaa I, Frazier K, et al. Effects of LX4211, a dual sodium-dependent glucose cotransporters 1 and 2 inhibitor, on postprandial glucose, insulin, glucagon-like peptide 1, and peptide tyrosine tyrosine in a dose-timing study in healthy subjects. Clin Ther. 2013;35:1162-1173.e8
28. 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.
29. 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.
30. 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.
31. Ljunggren Ö, Bolinder J, Johansson L, et al. Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin. Diabetes Obes Metab. 2012;14:990-999.
32. Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab Res Rev. 2005;21:31-38.
33. Rossetti L, Shulman GI, Zawalich W, DeFronzo RA. Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats. J Clin Invest. 1987;80:1037-1044.
34. Chao EC, Henry RR. SGLT2 inhibition–a novel strategy for diabetes treatment. Nat Rev Drug Discov. 2010;9:551-559.
35. Isaji M. SGLT2 inhibitors: molecular design and potential differences in effect. Kidney Int Suppl. 2011;120:S14-S19.
36. Janssen Pharmaceuticals, Inc. INVOKANA (canagliflozin) tablets, for oral use. Revised March 2016. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204042s011lbl.pdf. Accessed 1, April 2016.
37. AstraZeneca AB. Summary of product characteristics: dapagliflozin. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004161/WC500198486.pdf. Accessed March 23, 2016.
38. ® (dapagliflozin) tablets, for oral use. Revised December 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202293s008lbl.pdf. Accessed March 23, 2016.
39. Janssen-Cilag International NV. Summary of product characteristics: canagliflozin. Updated 13 January 2016. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002649/WC500156456.pdf. Accessed March 23, 2016.
40. Boehringer Ingelheim International GmbH. Summary of product characteristics: empagliflozin. Updated December 7, 2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002677/WC500168592.pdf. Accessed March 23, 2016.
41. ® (empagliflozin) tablets, for oral use. Updated March 18, 2016. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204629s005lbl.pdf. Accessed March 23, 2016.
42. Henry RR, Thakkar P, Tong C, et al. Efficacy and safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to insulin in patients with type 1 diabetes. Diabetes Care. 2015;38:2258–2265.
43. 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.
44. Pieber TR, Famulla S, Eilbracht J, et al. Empagliflozin as adjunct to insulin in patients with type 1 diabetes: a 4-week, randomized, placebo-controlled trial (EASE-1). Diabetes Obes Metab. 2015;17:928-935.
45. Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 2015;38:1638-1642.
46. Fitchett D, Zinman B, Wanner C, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME(R) trial. Eur Heart J. 2016;37:1526-1534.
47. 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;129:587-597.
48. Chilton R, Tikkanen I, Cannon CP, et al. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab. 2015;17:1180-1193.
49. Inzucchi SE, Zinman B, Wanner C, et al. SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res. 2015;12:90-100.
50. 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.e11
51. Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323-334.
52. Ptaszynska A, Johnsson KM, Parikh SJ, et al. Safety profile of dapagliflozin for type 2 diabetes: pooled analysis of clinical studies for overall safety and rare events. Drug Saf. 2014;37:815-829.
53. Heerspink HJ, Desai M, Jardine M, et al. Canagliflozin slows progression of renal function decline independently of glycemic effects. J Am Soc Nephrol. 2017;28:368-375.
54. Ferrannini E, Ramos SJ, Salsali A, et al. 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. 2010;33:2217-2224.
55. 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;1:208-219.
56. 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.
57. del Prato S, Nauck M, Durán-Garcia S, et al. Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data. Diabetes Obes Metab. 2015;17:581-590.
58. 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;37:1650-1659.
59. 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, double-blind, phase 3 trial. Lancet Diabetes Endocrinol. 2014;2:691-700.
60. Schumm-Draeger PM, Burgess L, Korányi L, et al. Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes: a 16-week randomized, placebo-controlled clinical trial. Diabetes Obes Metab. 2015;17:42-51.
61. Matthaei S, Bowering K, Rohwedder K, et al. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care. 2015;38:365-372.
62. 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.
63. Rosenstock J, Vico M, Wei L, et al. 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;35:1473-1478.
64. DeFronzo RA, Lewin A, Patel S, et al. Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes Care. 2015;38:384-393.
65. Jabbour SA, Hardy E, Sugg J, et al. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Diabetes Care. 2014;37:740-750.
66. Lewin A, DeFronzo RA, Patel S, et al. Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes. Diabetes Care. 2015;38:394-402.
67. 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.
68. Rosenstock J, Jelaska A, Zeller C, et al. Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78-week randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2015;17:936-948.
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;37:1815-1823.
70. 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.
71. 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.
72. Ji L, Ma J, Li H, et al. Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III study. Clin Ther. 2014;36:84-100.e9.
73. Kaku K, Maegawa H, Tanizawa Y, et al. Dapagliflozin as monotherapy or combination therapy in Japanese patients with type 2 diabetes: an open-label study. Diabetes Ther. 2014;5:415-433.
74. Nishimura R, Tanaka Y, Koiwai K, et al. Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, 4-week study. Cardiovasc Diabetol. 2015;14:11.
75. European Medicines Agency. Forxiga (dapagliflozin). EMA assessment report. Procedure no. EMEA/H/C/002322. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002322/WC500136024.pdf. Accessed September 17, 2013.
76. 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.
77. Kohan DE, Fioretto P, 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;85:962-971.
78. 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;15:463-473.
79. 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;2:369-384.
80. Bolinder J, Ljunggren Ö, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014;16:159-169.
81. Weir MR, Januszewicz A, Gilbert RE, et al. Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus. J Clin Hypertens. 2014;16:875-882.
82. Sjöström CD, Johansson P, Ptaszynska A, et al. Dapagliflozin lowers blood pressure in hypertensive and non-hypertensive patients with type 2 diabetes. Diab Vasc Dis Res. 2015;12:352-358.
83. Tikkanen I, Narko K, Zeller C, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015;38:420-428.
84. Amin NB, Wang X, Mitchell JR, et al. Blood pressure-lowering effect of the sodium glucose co-transporter-2 inhibitor ertugliflozin, assessed via ambulatory blood pressure monitoring in patients with type 2 diabetes and hypertension. Diabetes Obes Metab. 2015;17:805-808.
85. Kim SY, Guevara JP, Kim KM, et al. Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res. 2010;62:170-180.
86. Ptaszynska A, Hardy E, Johnsson E, et al. Effects of dapagliflozin on cardiovascular risk factors. Postgrad Med. 2013;125:181-189.
87. 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;67:1267-1282.
88. 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;36:2508-2515.
89. Kohler S, Salsali A, Hantel S, et al. Safety and tolerability of empagliflozin in patients with type 2 diabetes. Clin Ther. 2016;38:1299-1313.
90. US 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. Issued May 15, 2015. http://www.fda.gov/Drugs/DrugSafety/ucm475463.htm. Accessed March 16, 2016.
91. 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;37:1480-1483.
92. Taylor SI, Blau JE, Rother KI. SGLT2 inhibitors may predispose to ketoacidosis. J Clin Endocrinol Metab. 2015;100:2849-2852.
93. 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.
94. Johnsson KM, Ptaszynska A, Schmitz B, et al. Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J Diabetes Complications. 2013;27:479-484.
95. Johnsson KM, Ptaszynska A, Schmitz B, et al. Urinary tract infections in patients with diabetes treated with dapagliflozin. J Diabetes Complications. 2013;27:473-478.
96. Nicolle LE, Capuano G, Fung A, Usiskin K. Urinary tract infection in randomized phase III studies of canagliflozin, a sodium glucose co-transporter 2 inhibitor. Postgrad Med. 2014;126:7-17.
97. Nyirjesy P, Sobel JD, Fung A, et al. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. Curr Med Res Opin. 2014;30:1109-1119.
98. US Food and Drug Administration. Invokana (canagliflozin) tablets. NDA 204042. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM334550.pdf. Accessed 17 September 2013.
99. Barendse S, Singh H, Frier BM, Speight J. The impact of hypoglycaemia on quality of life and related patient-reported outcomes in type 2 diabetes: a narrative review. Diabet Med. 2012;29:293-302.
100. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care. 2013;36:1384-1395.
101. Häring HU, Merker L, Seewaldt-Becker E, et al. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2013;36:3396-3404.
102. Watts NB, Bilezikian JP, Usiskin K, et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2016;101:157-166.
103. Bilezikian JP, Watts NB, Usiskin K, et al. Evaluation of bone mineral density and bone biomarkers in patients with type 2 diabetes treated with canagliflozin. J Clin Endocrinol Metab. 2016;101:44-51.
104. Rodríguez-Gutiérrez R, Gonzalez-Saldivar G. Canagliflozin. Cleve Clin J Med. 2014;81:87-88.
105. US Food and Drug Administration. Dapagliflozin tablets, 5 and 10 mg. NDA 202293. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/ucm262994.pdf. Accessed September 17, 2013.
106. European Medicines Agency. Assessment Report: Jardiance (empagliflozin). March 20, 2014. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002677/WC500168594.pdf. Accessed March 17, 2016.
107. American Diabetes Association. Approaches to glycemic treatment. Sec. 7. In Standards of Medical Care in Diabetes – 2016. Diabetes Care. 2016;39:S52-S59.
108. 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.
109. Kasichayanula S, Liu X, Lacreta F, et al. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014;53:17-27.
110. Francke S, Mamidi RN, Solanki B, et al. In vitro metabolism of canagliflozin in human liver, kidney, intestine microsomes, and recombinant uridine diphosphate glucuronosyltransferases (UGT) and the effect of genetic variability of UGT enzymes on the pharmacokinetics of canagliflozin in humans. J Clin Pharmacol. 2015;55:1061-1072.
111. Lamos EM, Younk LM, Davis SN. Canagliflozin, an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus. Expert Opin Drug Metab Toxicol. 2013;9:763-775.
112. Chen LZ, Jungnik A, Mao Y, et al. Biotransformation and mass balance of the SGLT2 inhibitor empagliflozin in healthy volunteers. Xenobiotica. 2015;45:520-529.