Efficacy and safety of low-dose ipragliflozin, a selective sodium glucose transporter 2 inhibitor, in patients with type 2 diabetes mellitus
Corresponding Author(s) : Ichiro Abe
abe1ro@fukuoka-u.ac.jp
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 4 No. 3 (2016): 2016 Volume 4- Issue -3
Abstract
Few studies have focused on the efficacy and safety of low-dose of selective sodium glucose transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes. Ipragliflogin is an SGLT2 inhibitor licensed in Japan for administration at standard (50mg/day) or high (100mg/day) doses to treat type 2 diabetes mellitus in Japan. However, little is known about low-dose ipragliflozin (25mg/day) on safety and efficacy on the glucose control parameters and the other metabolic parameters. We study the efficacy and safety of low-dose ipragliflozin for the treatment of diabetic patients. Methods 14 individuals with type 2 diabetes mellitus who had not used SGLT2 inhibitors were recruited and given low-dose ipragliflozin (25mg/day). After 24 weeks, glucose control parameters and the other metabolic parameters were evaluated. Results All patients completed the study without any complications. Compared to baseline, HbA1c, fasting glucose, and HOMA ? significantly improved, and in terms of metabolic parameters, body weight, systolic blood pressure, LDL
cholesterol, and BNP significantly improved. In addition, urinary albumin excretion significantly reduced among the patients with microalbuminuria, and for one patient with macroalbuminuria, urinary albumin excretion decreased to half compared to baseline. Conclusion Low-dose ipragliflozin (25mg/day) is useful for treatment for type 2 diabetes mellitus on not only glycemic control but also the other metabolic disorders without complications of SGLT2 inhibitors.
Keywords
Selective sodium glucose transporter 2 inhibitors
Type 2 diabetes mellitus
1.
Ichiro Abe. Efficacy and safety of low-dose ipragliflozin, a selective sodium glucose transporter 2 inhibitor, in patients with type 2 diabetes mellitus. Int. J. of Allied Med. Sci. and Clin. Res. [Internet]. 2020 Aug. 6 [cited 2025 Oct. 26];4(3):376-82. Available from: https://ijamscr.com/ijamscr/article/view/283
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References
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Kanai Y, Lee WS, You G, et al. The human kidney low affinity Na+/glucose cotransporter SGLT2: delineation of the major renal reabsorptive mechanism for D glucose. J Clin Invest 93, 1994, 397 404. [2]. Wright EM. Renal Na glucose cotransporters. Am J Physiol Renal Physiol 280, 2001, 10 8. [3]. Neumiller JJ, White Jr JR, Campbell RK. Sodium glucose co transport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs 70, 2010, 377 85. [4]. Nair S, Wilding JP. Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab 95, 2010, 34 42. [5]. 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 97(3), 2012, 1020 31. [6]. Seufert J. SGLT2 inhibitors an insulin independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin. Diabetes Metab Syndr Obes 9(8), 2015, 543 54. [7]. Ohkura T. Ipragliflozin: A novel sodium glucose cotransporter 2 inhibitor developed in Japan. World J Diabetes 15 6(1), 2015, 136 44. [8]. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 373(22), 2015, 2117 28. [9]. Oliva RV, Bakris GL. Blood pressure effects of sodium glucose co transport 2 (SGLT2) inhibitors. J Am Soc Hypertens 8(5), 2014, 330 9. [10]. De Nicola L, Gabbai FB, Liberti ME, et al. Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy: targeting the renal tubule in diabetes. Am J Kidney Dis 64(1), 2014, 16 24. [11]. Taylor SI, Blau JE, Rother KI. SGLT2 Inhibitors May Predispose to Ketoacidosis. J Clin Endocrinol Metab 100(8), 2015, 2849 52. [12]. Nauck MA. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther 11(8), 2014, 1335 80. [13]. Zimmet P, Alberti KGMM, Shaw J. Global and societal implications of the diabetes epidemic. Nature 414(6865), 2001, 782 7. [14]. Edelman SV. Importance of glucose control. Med Clin North Am 82(4), 1998, 665 687. [15]. Virally M, Blicklé JF, Girard J, et al. Type 2 diabetes mellitus: epidemiology, pathophysiology, unmet needs and therapeutical perspectives. Diabetes Metab 33(4), 2007, 231 244. [16]. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia 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). Diabetologia 55(6), 2012, 577 96. [17]. Takahara M, Shiraiwa T, Matsuoka TA, et al. Ameliorated pancreatic ? cell dysfunction in type 2 diabetic patients treated with a sodium glucose cotransporter 2 inhibitor ipragliflozin. Endocr J 62(1), 2015, 7 86.
Ichiro Abe et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-4(3) 2016 [376-382]
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[18]. Macdonald FR, Peel JE, Jones HB, et al. The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats. Diabetes Obes Metab 12(11), 2010, 1004--12. [19]. Polidori D, Mari A, Ferrannini E. Canagliflozin, a sodium glucose co--transporter 2 inhibitor, improves model--based indices of beta cell function in patients with type 2 diabetes. Diabetologia 57(5), 2014, 891--901. [20]. Tahara A, Kurosaki E, Yokono M, et al. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 715(1--3), 2013, 246--55. [21]. Inagaki N, Goda M, Yokota S, et al. Effects of Baseline Blood Pressure and Low--Density Lipoprotein Cholesterol on Safety and Efficacy of Canagliflozin in Japanese Patients with Type 2 Diabetes Mellitus. Adv Ther 32(11), 2015, 1085--103. [22]. 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 139(1), 2013, 51--9. [23]. Scheen AJ. Pharmacodynamics, efficacy and safety of sodium--glucose co--transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs 75(1), 2015, 33--59
References
Kanai Y, Lee WS, You G, et al. The human kidney low affinity Na+/glucose cotransporter SGLT2: delineation of the major renal reabsorptive mechanism for D glucose. J Clin Invest 93, 1994, 397 404. [2]. Wright EM. Renal Na glucose cotransporters. Am J Physiol Renal Physiol 280, 2001, 10 8. [3]. Neumiller JJ, White Jr JR, Campbell RK. Sodium glucose co transport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs 70, 2010, 377 85. [4]. Nair S, Wilding JP. Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab 95, 2010, 34 42. [5]. 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 97(3), 2012, 1020 31. [6]. Seufert J. SGLT2 inhibitors an insulin independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin. Diabetes Metab Syndr Obes 9(8), 2015, 543 54. [7]. Ohkura T. Ipragliflozin: A novel sodium glucose cotransporter 2 inhibitor developed in Japan. World J Diabetes 15 6(1), 2015, 136 44. [8]. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 373(22), 2015, 2117 28. [9]. Oliva RV, Bakris GL. Blood pressure effects of sodium glucose co transport 2 (SGLT2) inhibitors. J Am Soc Hypertens 8(5), 2014, 330 9. [10]. De Nicola L, Gabbai FB, Liberti ME, et al. Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy: targeting the renal tubule in diabetes. Am J Kidney Dis 64(1), 2014, 16 24. [11]. Taylor SI, Blau JE, Rother KI. SGLT2 Inhibitors May Predispose to Ketoacidosis. J Clin Endocrinol Metab 100(8), 2015, 2849 52. [12]. Nauck MA. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther 11(8), 2014, 1335 80. [13]. Zimmet P, Alberti KGMM, Shaw J. Global and societal implications of the diabetes epidemic. Nature 414(6865), 2001, 782 7. [14]. Edelman SV. Importance of glucose control. Med Clin North Am 82(4), 1998, 665 687. [15]. Virally M, Blicklé JF, Girard J, et al. Type 2 diabetes mellitus: epidemiology, pathophysiology, unmet needs and therapeutical perspectives. Diabetes Metab 33(4), 2007, 231 244. [16]. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia 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). Diabetologia 55(6), 2012, 577 96. [17]. Takahara M, Shiraiwa T, Matsuoka TA, et al. Ameliorated pancreatic ? cell dysfunction in type 2 diabetic patients treated with a sodium glucose cotransporter 2 inhibitor ipragliflozin. Endocr J 62(1), 2015, 7 86.
Ichiro Abe et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-4(3) 2016 [376-382]
382
[18]. Macdonald FR, Peel JE, Jones HB, et al. The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats. Diabetes Obes Metab 12(11), 2010, 1004--12. [19]. Polidori D, Mari A, Ferrannini E. Canagliflozin, a sodium glucose co--transporter 2 inhibitor, improves model--based indices of beta cell function in patients with type 2 diabetes. Diabetologia 57(5), 2014, 891--901. [20]. Tahara A, Kurosaki E, Yokono M, et al. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 715(1--3), 2013, 246--55. [21]. Inagaki N, Goda M, Yokota S, et al. Effects of Baseline Blood Pressure and Low--Density Lipoprotein Cholesterol on Safety and Efficacy of Canagliflozin in Japanese Patients with Type 2 Diabetes Mellitus. Adv Ther 32(11), 2015, 1085--103. [22]. 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 139(1), 2013, 51--9. [23]. Scheen AJ. Pharmacodynamics, efficacy and safety of sodium--glucose co--transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs 75(1), 2015, 33--59
centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 55(6), 2012, 577 96. [17]. Takahara M, Shiraiwa T, Matsuoka TA, et al. Ameliorated pancreatic ? cell dysfunction in type 2 diabetic patients treated with a sodium glucose cotransporter 2 inhibitor ipragliflozin. Endocr J 62(1), 2015, 7 86.
Ichiro Abe et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-4(3) 2016 [376-382]
382
[18]. Macdonald FR, Peel JE, Jones HB, et al. The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats. Diabetes Obes Metab 12(11), 2010, 1004--12. [19]. Polidori D, Mari A, Ferrannini E. Canagliflozin, a sodium glucose co--transporter 2 inhibitor, improves model--based indices of beta cell function in patients with type 2 diabetes. Diabetologia 57(5), 2014, 891--901. [20]. Tahara A, Kurosaki E, Yokono M, et al. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 715(1--3), 2013, 246--55. [21]. Inagaki N, Goda M, Yokota S, et al. Effects of Baseline Blood Pressure and Low--Density Lipoprotein Cholesterol on Safety and Efficacy of Canagliflozin in Japanese Patients with Type 2 Diabetes Mellitus. Adv Ther 32(11), 2015, 1085--103. [22]. 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 139(1), 2013, 51--9. [23]. Scheen AJ. Pharmacodynamics, efficacy and safety of sodium--glucose co--transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs 75(1), 2015, 33--59