Login Register Cart 0
Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Structural Perspectives and Advancement of SGLT2 Inhibitors for the Treatment of Type 2 Diabetes

Author(s): Shivani Sharma, Amit Mittal*, Shubham Kumar and Anu Mittal

Volume 18, Issue 6, 2022

Published on: 07 January, 2022

Article ID: e170921196601 Pages: 23

DOI: 10.2174/1573399817666210917122745

Price: $65

Abstract

Diabetes mellitus is an ailment that affects a large number of individuals worldwide and its pervasiveness has been predicted to increase later on. Every year, billions of dollars are spent globally on diabetes-related health care practices. Contemporary hyperglycemic therapies to rationalize Type 2 Diabetes Mellitus (T2DM) mostly involve pathways that are insulin-dependent and lack effectiveness as the pancreas’ β-cell function declines more significantly. Homeostasis via kidneys emerges as a new and future strategy to minimize T2DM complications. This article covers the reabsorption of glucose mechanism in the kidneys, the functional mechanism of various Sodium- Glucose Cotransporter 2 (SGLT2) inhibitors, their structure and driving profile, and a few SGLT2 inhibitors now accessible in the market as well as those in different periods of advancement. The advantages of SGLT2 inhibitors are dose-dependent glycemic regulation changes with a significant reduction both in the concentration of HbA1c and body weight clinically and statistically. A considerable number of SGLT2 inhibitors have been approved by the FDA, while a few others, still in preliminaries, have shown interesting effects.

Keywords: SGLT2 Inhibitors, diabetes mellitus, dapagliflozin, glucose, hypoglycemia, phlorizin.

[1]
Saeedi P, Salpea P, Karuranga S, et al. Mortality attributable to diabetes in 20-79years old adults, 2019 estimates: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2020; 162: 108086.
[http://dx.doi.org/10.1016/j.diabres.2020.108086] [PMID: 32068099]
[2]
Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2019; 157: 107843.
[http://dx.doi.org/10.1016/j.diabres.2019.107843] [PMID: 31518657]
[3]
WHO Global health expenditure database. Geneva. Available from: https://apps.who.int/nha/database
[4]
Williams R, Karuranga S, Malanda B, et al. Global and regional estimates and projections of diabetes-related health expenditure: Results from the international diabetes federation diabetes atlas, 9th edition. Diabetes Res Clin Pract 2020; 162: 108072.
[http://dx.doi.org/10.1016/j.diabres.2020.108072] [PMID: 32061820]
[5]
Shah BR, Hux JE, Laupacis A, Zinman B, van Walraven C. Clinical inertia in response to inadequate glycemic control: Do specialists differ from primary care physicians? Diabetes Care 2005; 28(3): 600-6.
[http://dx.doi.org/10.2337/diacare.28.3.600] [PMID: 15735195]
[6]
Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009; 32(1): 193-203.
[http://dx.doi.org/10.2337/dc08-9025] [PMID: 18945920]
[7]
Nowicka P, Santoro N, Liu H, de Romualdo L. Classification and diagnosis of diabetes. Diabetes Care 2015; 38(Suppl.): S8-S16.
[http://dx.doi.org/10.2337/dc15-S005] [PMID: 25537714]
[8]
WHO/IDF. Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. Report of a WHO/IDFConsultation. Geneva 2016. Available from: https://www.semanticscholar.org/paper/Definition-and-Diagnosis-of-Diabetes-Mellitus-and-a/78e057c984ae6fa2120ab36fe33be5d776177062
[9]
American Diabetes Association. Classification and diagnosis of diabetes: Standards of medical care in diabetes – 2018. Diabetes Care 2018; 41(Suppl. 1): S13-27.
[http://dx.doi.org/10.2337/dc18-S002] [PMID: 29222373]
[10]
Kaur P, Mittal A, Nayak SK, Vyas M, Mishra V, Khatik GL. Current strategies and drug targets in the management of type 2 diabetes mellitus. Curr Drug Targets 2018; 19(15): 1738-66.
[http://dx.doi.org/10.2174/1389450119666180727142902] [PMID: 30051787]
[11]
Ramachandran U, Kumar R, Mittal A. Fine tuning of PPAR ligands for type 2 diabetes and metabolic syndrome. Mini Rev Med Chem 2006; 6(5): 563-73.
[http://dx.doi.org/10.2174/138955706776876140] [PMID: 16719831]
[12]
Kumar R, Mittal A, Ramachandran U. Design and synthesis of 6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid derivatives as PPARgamma activators. Bioorg Med Chem Lett 2007; 17(16): 4613-8.
[http://dx.doi.org/10.1016/j.bmcl.2007.05.081] [PMID: 17574414]
[13]
Bharatam PV, Patel DS, Adane L, Mittal A, Sundriyal S. Modeling and informatics in designing anti-diabetic agents. Curr Pharm Des 2007; 13(34): 3518-30.
[http://dx.doi.org/10.2174/138161207782794239] [PMID: 18220788]
[14]
Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: Therapeutic implications. Diabet Med 2010; 27(2): 136-42.
[http://dx.doi.org/10.1111/j.1464-5491.2009.02894.x] [PMID: 20546255]
[15]
You G, Lee W-S, Barros EJ, et al. Molecular characteristics of Na(+)-coupled glucose transporters in adult and embryonic rat kidney. J Biol Chem 1995; 270(49): 29365-71.
[http://dx.doi.org/10.1074/jbc.270.49.29365] [PMID: 7493971]
[16]
Lee YJ, Lee YJ, Han HJ. Regulatory mechanisms of Na(+)/glucose cotransporters in renal proximal tubule cells. Kidney Int Suppl 2007; 72(106): S27-35.
[http://dx.doi.org/10.1038/sj.ki.5002383] [PMID: 17653207]
[17]
Amsler K, Cook JS. Development of Na+-dependent hexose transport in a cultured line of porcine kidney cells. Am J Physiol 1982; 242(1): C94-C101.
[http://dx.doi.org/10.1152/ajpcell.1982.242.1.C94] [PMID: 6277200]
[18]
Bays H. Sodium glucose co-transporter type 2 (SGLT2) inhibitors: Targeting the kidney to improve glycemic control in diabetes mellitus. Diabetes Ther 2013; 4(2): 195-220.
[http://dx.doi.org/10.1007/s13300-013-0042-y] [PMID: 24142577]
[19]
Mackenzie B, Panayotova-Heiermann M, Loo DD, Lever JE, Wright EM. SAAT1 is a low affinity Na+/glucose cotransporter and not an amino acid transporter. A reinterpretation. J Biol Chem 1994; 269(36): 22488-91.
[http://dx.doi.org/10.1016/S0021-9258(17)31672-1] [PMID: 8077195]
[20]
Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 2005; 54(12): 3427-34.
[http://dx.doi.org/10.2337/diabetes.54.12.3427] [PMID: 16306358]
[21]
Turk E, Martín MG, Wright EM. Structure of the human Na+/glucose cotransporter gene SGLT1. J Biol Chem 1994; 269(21): 15204-9.
[http://dx.doi.org/10.1016/S0021-9258(17)36592-4] [PMID: 8195156]
[22]
Brown GK. Glucose transporters: structure, function and consequences of deficiency. J Inherit Metab Dis 2000; 23(3): 237-46.
[http://dx.doi.org/10.1023/A:1005632012591] [PMID: 10863940]
[23]
Wright EM, Turk E. The sodium/glucose cotransport family SLC5. Pflugers Arch 2004; 447(5): 510-8.
[http://dx.doi.org/10.1007/s00424-003-1202-0] [PMID: 12748858]
[24]
Kanai Y, Lee WS, You G, Brown D, Hediger MA. The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Invest 1994; 93(1): 397-404.
[http://dx.doi.org/10.1172/JCI116972] [PMID: 8282810]
[25]
Lee WS, Kanai Y, Wells RG, Hediger MA. The high affinity Na+/glucose cotransporter. Re-evaluation of function and distribution of expression. J Biol Chem 1994; 269(16): 12032-9.
[http://dx.doi.org/10.1016/S0021-9258(17)32677-7] [PMID: 8163506]
[26]
List JF, Whaley JM. Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney Int Suppl 2011; 79(120): S20-7.
[http://dx.doi.org/10.1038/ki.2010.512] [PMID: 21358698]
[27]
Pan X, Huan Y, Shen Z, Liu Z. Synthesis and biological evaluation of novel tetrahydroisoquinoline-C-aryl glucosides as SGLT2 inhibitors for the treatment of type 2 diabetes. Eur J Med Chem 2016; 114: 89-100.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.053] [PMID: 26974378]
[28]
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(1): 101-9.
[http://dx.doi.org/10.3109/00365517109090668] [PMID: 5093515]
[29]
Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus: Systematic review and meta-analysis of cardiovascular outcomes trials. Circulation 2019; 139(17): 2022-31.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038868] [PMID: 30786725]
[30]
Nespoux J, Vallon V. SGLT2 inhibition and kidney protection. Clin Sci (Lond) 2018; 132(12): 1329-39.
[http://dx.doi.org/10.1042/CS20171298] [PMID: 29954951]
[31]
Nespoux J, Vallon V. Renal effects of SGLT2 inhibitors: an update. Curr Opin Nephrol Hypertens 2020; 29(2): 190-8.
[http://dx.doi.org/10.1097/MNH.0000000000000584] [PMID: 31815757]
[32]
Bonora BM, Avogaro A, Fadini GP. Extraglycemic effects of SGLT2 inhibitors: A review of the evidence. Diabetes Metab Syndr Obes 2020; 13: 161-74.
[http://dx.doi.org/10.2147/DMSO.S233538] [PMID: 32021362]
[33]
Xiang B, Zhao X, Zhou X. Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in diabetic and nondiabetic patients. Cardiovasc Diabetol 2021; 20(1): 78.
[http://dx.doi.org/10.1186/s12933-021-01266-x] [PMID: 33827579]
[34]
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377(7): 644-57.
[http://dx.doi.org/10.1056/NEJMoa1611925] [PMID: 28605608]
[35]
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22): 2117-28.
[http://dx.doi.org/10.1056/NEJMoa1504720] [PMID: 26378978]
[36]
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380(4): 347-57.
[http://dx.doi.org/10.1056/NEJMoa1812389] [PMID: 30415602]
[37]
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380(24): 2295-306.
[http://dx.doi.org/10.1056/NEJMoa1811744] [PMID: 30990260]
[38]
Kluger AY, Tecson KM, Barbin CM, et al. Cardiorenal outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME trials: A systematic review. Rev Cardiovasc Med 2018; 19(2): 41-9.
[PMID: 31032602]
[39]
Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375(4): 323-34.
[http://dx.doi.org/10.1056/NEJMoa1515920] [PMID: 27299675]
[40]
Mahaffey KW, Jardine MJ, Bompoint S, et al. Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes mellitus and chronic kidney disease in primary and secondary cardiovascular prevention groups: Results from the randomized CREDENCE trial. Circulation 2019; 140(9): 739-50.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042007] [PMID: 31291786]
[41]
Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019; 393(10166): 31-9.
[http://dx.doi.org/10.1016/S0140-6736(18)32590-X] [PMID: 30424892]
[42]
Mosenzon O, Wiviott SD, Cahn A, et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: An analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol 2019; 7(8): 606-17.
[http://dx.doi.org/10.1016/S2213-8587(19)30180-9] [PMID: 31196815]
[43]
Petersen C. Analyse des phloridzins. Ann Phar 1835; 15(2): 178-8.
[http://dx.doi.org/10.1002/jlac.18350150210]
[44]
De Koninck L. Observations sur les proprietes febrifuges de lasphloridzine. Bull Soc Med Gand 1836; 1: 75-110.
[45]
Merck E. Verzeichniss sammtlicher praparate und drogen. Merck.Archives. Darmstadt, Germany 1885; pp. 67-7.
[46]
Keller DM, Lotspeich WD. Effect of phlorizin on the osmotic behavior of mitochondria in isotonic sucrose. J Biol Chem 1959; 234(4): 991-4.
[http://dx.doi.org/10.1016/S0021-9258(18)70217-2] [PMID: 13654305]
[47]
Alvarado F, Crane RK. Phlorizin as a competitive inhibitor of the active transport of sugars by hamster small intestine, in vitro. Biochim Biophys Acta 1962; 56: 170-2.
[http://dx.doi.org/10.1016/0006-3002(62)90543-7] [PMID: 13860792]
[48]
Panten U, Schwanstecher M, Schwanstecher C. Sulfonylurea receptors and mechanism of sulfonylurea action. Exp Clin Endocrinol Diabetes 1996; 104(1): 1-9.
[http://dx.doi.org/10.1055/s-0029-1211414] [PMID: 8750563]
[49]
Bailey CJ. Biguanides and NIDDM. Diabetes Care 1992; 15(6): 755-72.
[http://dx.doi.org/10.2337/diacare.15.6.755] [PMID: 1600835]
[50]
Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 2000; 348(Pt 3): 607-14.
[http://dx.doi.org/10.1042/bj3480607] [PMID: 10839993]
[51]
Musi N, Hirshman MF, Nygren J, et al. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 2002; 51(7): 2074-81.
[http://dx.doi.org/10.2337/diabetes.51.7.2074] [PMID: 12086935]
[52]
Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med 2002; 137(1): 25-33.
[http://dx.doi.org/10.7326/0003-4819-137-1-200207020-00009] [PMID: 12093242]
[53]
Quianzon CC, Cheikh IE. History of current non-insulin medications for diabetes mellitus. J Community Hosp Intern Med Perspect 2012; 2(3): 10-0.
[http://dx.doi.org/10.3402/jchimp.v2i3.19081] [PMID: 23882374]
[54]
White J, Campbell R, White J. Overview of the medications used to treat type 2 diabetes.Medications for the Treatment of Diabetes. Montvale, NJ: American Diabetes Association/Thomson Reuters 2008; pp. 5-15.
[55]
van de Laar FA, Lucassen PL, Akkermans RP, van de Lisdonk EH, Rutten GE, van Weel C. α-glucosidase inhibitors for patients with type 2 diabetes: Results from a Cochrane systematic review and meta-analysis. Diabetes Care 2005; 28(1): 154-63.
[http://dx.doi.org/10.2337/diacare.28.1.154] [PMID: 15616251]
[56]
van de Laar FA. Alpha-glucosidase inhibitors in the early treatment of type 2 diabetes. Vasc Health Risk Manag 2008; 4(6): 1189-95.
[http://dx.doi.org/10.2147/VHRM.S3119] [PMID: 19337532]
[57]
Campbell LK, White JR, Campbell RK. Acarbose: Its role in the treatment of diabetes mellitus. Ann Pharmacother 1996; 30(11): 1255-62.
[http://dx.doi.org/10.1177/106002809603001110] [PMID: 8913408]
[58]
Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 1996; 45(12): 1661-9.
[http://dx.doi.org/10.2337/diab.45.12.1661] [PMID: 8922349]
[59]
Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: A consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care 2004; 27(1): 256-63.
[http://dx.doi.org/10.2337/diacare.27.1.256] [PMID: 14693998]
[60]
Desai RC, Han W, Metzger EJ, et al. 5-aryl thiazolidine-2,4- diones: discovery of PPAR dual α/γ agonists as antidiabetic agents. Bioorg Med Chem Lett 2003; 13(16): 2795-8.
[http://dx.doi.org/10.1016/S0960-894X(03)00505-5] [PMID: 12873517]
[61]
Landgraf R. Meglitinide analogues in the treatment of type 2 diabetes mellitus. Drugs Aging 2000; 17(5): 411-25.
[http://dx.doi.org/10.2165/00002512-200017050-00007] [PMID: 11190420]
[62]
Melander A. Kinetics-effect relations of insulin-releasing drugs in patients with type 2 diabetes: Brief overview. Diabetes 2004; 53(Suppl. 3): S151-5.
[http://dx.doi.org/10.2337/diabetes.53.suppl_3.S151] [PMID: 15561903]
[63]
Hansen KB, Vilsbøll T, Knop FK. Incretin mimetics: A novel therapeutic option for patients with type 2 diabetes - A review. Diabetes Metab Syndr Obes 2010; 3: 155-63.
[http://dx.doi.org/10.2147/DMSO.S7004] [PMID: 21437085]
[64]
Drucker DJ, Nauck MA. The incretin system: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006; 368(9548): 1696-705.
[http://dx.doi.org/10.1016/S0140-6736(06)69705-5] [PMID: 17098089]
[65]
Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006; 49(11): 2564-71.
[http://dx.doi.org/10.1007/s00125-006-0416-z] [PMID: 17001471]
[66]
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 2012; 55(6): 1577-96.
[http://dx.doi.org/10.1007/s00125-012-2534-0] [PMID: 22526604]
[67]
Bailey CJ. Renal glucose reabsorption inhibitors to treat diabetes. Trends Pharmacol Sci 2011; 32(2): 63-71.
[http://dx.doi.org/10.1016/j.tips.2010.11.011] [PMID: 21211857]
[68]
Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in management of diabetes. Lancet Diabetes Endocrinol 2013; 1(2): 140-51.
[http://dx.doi.org/10.1016/S2213-8587(13)70050-0] [PMID: 24622320]
[69]
Kees KL, Fitzgerald JJ Jr, Steiner KE, et al. New potent antihyperglycemic agents in db/db mice: Synthesis and structure-activity relationship studies of (4-substituted benzyl) (trifluoromethyl)pyrazoles and -pyrazolones. J Med Chem 1996; 39(20): 3920-8.
[http://dx.doi.org/10.1021/jm960444z] [PMID: 8831758]
[70]
Ohsumi K, Matsueda H, Hatanaka T, et al. Pyrazole-O-glucosides as novel Na(+)-glucose cotransporter (SGLT) inhibitors. Bioorg Med Chem Lett 2003; 13(14): 2269-72.
[http://dx.doi.org/10.1016/S0960-894X(03)00466-9] [PMID: 12824015]
[71]
Tsujihara K, Hongu M, Saito K, et al. Na(+)-glucose cotransporter (SGLT) inhibitors as antidiabetic agents. 4. Synthesis and pharmacological properties of 4′-dehydroxyphlorizin derivatives substituted on the B ring. J Med Chem 1999; 42(26): 5311-24.
[http://dx.doi.org/10.1021/jm990175n] [PMID: 10639275]
[72]
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(9): 1794-800.
[http://dx.doi.org/10.2337/diabetes.48.9.1794] [PMID: 10480610]
[73]
Oku A, Ueta K, Nawano M, et al. Antidiabetic effect of T-1095, an inhibitor of Na(+)-glucose cotransporter, in neonatally streptozotocin-treated rats. Eur J Pharmacol 2000; 391(1-2): 183-92.
[http://dx.doi.org/10.1016/S0014-2999(00)00016-9] [PMID: 10720650]
[74]
Nawano M, Oku A, Ueta K, et al. Hyperglycemia contributes insulin resistance in hepatic and adipose tissue but not skeletal muscle of ZDF rats. Am J Physiol Endocrinol Metab 2000; 278(3): E535-43.
[http://dx.doi.org/10.1152/ajpendo.2000.278.3.E535] [PMID: 10710509]
[75]
Fujimoto Y, Torres TP, Donahue EP, Shiota M. Glucose toxicity is responsible for the development of impaired regulation of endogenous glucose production and hepatic glucokinase in Zucker diabetic fatty rats. Diabetes 2006; 55(9): 2479-90.
[http://dx.doi.org/10.2337/db05-1511] [PMID: 16936196]
[76]
Nunoi K, Yasuda K, Adachi T, et al. Beneficial effect of T-1095, a selective inhibitor of renal Na+-glucose cotransporters, on metabolic index and insulin secretion in spontaneously diabetic GK rats. Clin Exp Pharmacol Physiol 2002; 29(5-6): 386-90.
[http://dx.doi.org/10.1046/j.1440-1681.2002.03671.x] [PMID: 12010180]
[77]
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(2): 578-86.
[http://dx.doi.org/10.1038/sj.bjp.0703829] [PMID: 11159708]
[78]
Ueta K, Ishihara T, Matsumoto Y, et al. Long-term treatment with the Na+-glucose cotransporter inhibitor T-1095 causes sustained improvement in hyperglycemia and prevents diabetic neuropathy in Goto-Kakizaki Rats. Life Sci 2005; 76(23): 2655-68.
[http://dx.doi.org/10.1016/j.lfs.2004.09.038] [PMID: 15792833]
[79]
Isaji M. SGLT2 inhibitors: Molecular design and potential differences in effect. Kidney Int Suppl 2011; 79(120): S14-9.
[http://dx.doi.org/10.1038/ki.2010.511] [PMID: 21358697]
[80]
Katsuno K, Fujimori Y, Takemura Y, et al. Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level. J Pharmacol Exp Ther 2007; 320(1): 323-30.
[http://dx.doi.org/10.1124/jpet.106.110296] [PMID: 17050778]
[81]
Hussey EK, Dobbins RL, Stolz RR, et al. A double-blind randomized repeat dose study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of three times daily dosing of sergliflozin, a novel inhibitor of renal glucose reabsorption, in healthy overweight and obese subjects. Diabetes 2007; 56: A491-1.
[82]
Ikegai K, Imamura M, Suzuki T, et al. Synthesis and biological evaluation of C-glucosides with azulene rings as selective SGLT2 inhibitors for the treatment of type 2 diabetes mellitus: Discovery of YM543. Bioorg Med Chem 2013; 21(13): 3934-48.
[http://dx.doi.org/10.1016/j.bmc.2013.03.067] [PMID: 23651509]
[83]
Meng W, Ellsworth BA, Nirschl AA, et al. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem 2008; 51(5): 1145-9.
[http://dx.doi.org/10.1021/jm701272q] [PMID: 18260618]
[84]
Han S, Hagan DL, Taylor JR, et al. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes 2008; 57(6): 1723-9.
[http://dx.doi.org/10.2337/db07-1472] [PMID: 18356408]
[85]
Anderson SL. Dapagliflozin efficacy and safety: A perspective review. Ther Adv Drug Saf 2014; 5(6): 242-54.
[http://dx.doi.org/10.1177/2042098614551938] [PMID: 25436106]
[86]
Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther 2009; 85(5): 513-9.
[http://dx.doi.org/10.1038/clpt.2008.250] [PMID: 19129749]
[87]
Saeed MA, Narendran P. Dapagliflozin for the treatment of type 2 diabetes: A review of the literature. Drug Des Devel Ther 2014; 8: 2493-505.
[PMID: 25525338]
[88]
Kohan DE, Fioretto P, Johnsson K, Parikh S, Ptaszynska A, Ying L. The effect of dapagliflozin on renal function in patients with type 2 diabetes. J Nephrol 2016; 29(3): 391-400.
[http://dx.doi.org/10.1007/s40620-016-0261-1] [PMID: 26894924]
[89]
Hinnen D. Glucuretic effects and renal safety of dapagliflozin in patients with type 2 diabetes. Ther Adv Endocrinol Metab 2015; 6(3): 92-102.
[http://dx.doi.org/10.1177/2042018815575273] [PMID: 26137213]
[90]
Sarnoski-Brocavich S, Hilas O. Canagliflozin (invokana), a novel oral agent for type-2 diabetes. P&T 2013; 38(11): 656-66.
[PMID: 24391386]
[91]
Mizerski G, Kicinski P, Jaroszynski A. Flozins, inhibitors of type 2 renal sodium-glucose co-transporter–not only antihyperglycemic drugs. Curr Issues Pharm Med Sci 2015; 28(3): 155-8.
[http://dx.doi.org/10.1515/cipms-2015-0063]
[92]
Koga Y, Sakamaki S, Hongu M, et al. C-Glucosides with heteroaryl thiophene as novel sodium-dependent glucose cotransporter 2 inhibitors. Bioorg Med Chem 2013; 21(17): 5561-72.
[http://dx.doi.org/10.1016/j.bmc.2013.05.048] [PMID: 23809172]
[93]
Kumar S, Khatik GL, Mittal A. Recent developments in sodium-glucose co-transporter 2 (sglt2) inhibitors as a valuable tool in the treatment of type 2 diabetes mellitus. Mini Rev Med Chem 2020; 20(3): 170-82.
[http://dx.doi.org/10.2174/1389557519666191009163519] [PMID: 32134370]
[94]
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): 539-45.
[http://dx.doi.org/10.1111/j.1463-1326.2012.01558.x] [PMID: 22226086]
[95]
Devineni D, Polidori D, Curtin C, Stieltjes H, Tian H, Wajs E. Single-dose pharmacokinetics and pharmacodynamics of canagliflozin, a selective inhibitor of sodium glucose cotransporter 2, in healthy indian participants. Clin Ther 2016; 38(1): 89-98.e1.
[http://dx.doi.org/10.1016/j.clinthera.2015.11.008] [PMID: 26687552]
[96]
Miao Z, Nucci G, Amin N, et al. Pharmacokinetics, metabolism, and excretion of the antidiabetic agent ertugliflozin (PF-04971729) in healthy male subjects. Drug Metab Dispos 2013; 41(2): 445-56.
[http://dx.doi.org/10.1124/dmd.112.049551] [PMID: 23169609]
[97]
Mascitti V, Maurer TS, Robinson RP, et al. Discovery of a clinical candidate from the structurally unique dioxa-bicyclo[3.2.1]octane class of sodium-dependent glucose cotransporter 2 inhibitors. J Med Chem 2011; 54(8): 2952-60.
[http://dx.doi.org/10.1021/jm200049r] [PMID: 21449606]
[98]
Kovacs CS, Seshiah V, Swallow R, et al. investigators, E.R.P.t.. 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(2): 147-58.
[http://dx.doi.org/10.1111/dom.12188] [PMID: 23906415]
[99]
Scott LJ. Empagliflozin: A review of its use in patients with type 2 diabetes mellitus. Drugs 2014; 74(15): 1769-84.
[http://dx.doi.org/10.1007/s40265-014-0298-1] [PMID: 25274537]
[100]
Heise T, Seewaldt-Becker E, Macha S, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks’ treatment with empagliflozin once daily in patients with type 2 diabetes. Diabetes Obes Metab 2013; 15(7): 613-21.
[http://dx.doi.org/10.1111/dom.12073] [PMID: 23356556]
[101]
Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 2014; 124(2): 499-508.
[http://dx.doi.org/10.1172/JCI72227] [PMID: 24463454]
[102]
Al Jobori H, Daniele G, Adams J, et al. Empagliflozin treatment is associated with improved β-cell function in type 2 diabetes mellitus. J Clin Endocrinol Metab 2018; 103(4): 1402-7.
[http://dx.doi.org/10.1210/jc.2017-01838] [PMID: 29342295]
[103]
Riggs MM, Seman LJ, Staab A, et al. Exposure-response modelling for empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes. Br J Clin Pharmacol 2014; 78(6): 1407-18.
[http://dx.doi.org/10.1111/bcp.12453] [PMID: 24964723]
[104]
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(12): 1180-93.
[http://dx.doi.org/10.1111/dom.12572] [PMID: 26343814]
[105]
Markham A. Remogliflozin Etabonate: First Global Approval. Drugs 2019; 79(10): 1157-61.
[http://dx.doi.org/10.1007/s40265-019-01150-9] [PMID: 31201711]
[106]
GlenmarkPharmaceuticals Glenmark launches novel, globally researched anti-diabetes drug remogliflozin in India. 2019. Available from: swire.com/in/news-releases/glenmark -launches-novel -globally-researched -anti-diabetes -drug-remogliflozin-in-india -80661 4073.html(30 Apr 2019.)
[107]
Fujimori Y, Katsuno K, Nakashima I, Ishikawa-Takemura Y, Fujikura H, Isaji M. Remogliflozin etabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther 2008; 327(1): 268-76.
[http://dx.doi.org/10.1124/jpet.108.140210] [PMID: 18583547]
[108]
Markham A, Elkinson S. Luseogliflozin: first global approval. Drugs 2014; 74(8): 945-50.
[http://dx.doi.org/10.1007/s40265-014-0230-8] [PMID: 24848756]
[109]
Sakai S, Kaku K, Seino Y, et al. Efficacy and safety of the SGLT2 inhibitor luseogliflozin in Japanese patients with type 2 diabetes mellitus stratified according to baseline body mass index: pooled analysis of data from 52-week phase III trials. Clin Ther 2016; 38(4): 843-862.e9.
[http://dx.doi.org/10.1016/j.clinthera.2016.01.017] [PMID: 27021608]
[110]
Kakinuma H, Oi T, Hashimoto-Tsuchiya Y, et al. (1S)-1,5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D-glucitol (TS-071) is a potent, selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes treatment. J Med Chem 2010; 53(8): 3247-61.
[http://dx.doi.org/10.1021/jm901893x] [PMID: 20302302]
[111]
Samukawa Y, Haneda M, Seino Y, et al. Pharmacokinetics and pharmacodynamics of luseogliflozin, a selective SGLT2 inhibitor, in Japanese patients with type 2 diabetes with mild to severe renal impairment. Clin Pharmacol Drug Dev 2018; 7(8): 820-8.
[http://dx.doi.org/10.1002/cpdd.456] [PMID: 29693800]
[112]
Imamura M, Nakanishi K, Suzuki T, et al. Discovery of Ipragliflozin (ASP1941): a novel C-glucoside with benzothiophene structure as a potent and selective sodium glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes mellitus. Bioorg Med Chem 2012; 20(10): 3263-79.
[http://dx.doi.org/10.1016/j.bmc.2012.03.051] [PMID: 22507206]
[113]
Tahara A, Takasu T, Yokono M, Imamura M, Kurosaki E. Antidiabetic and antiobesity effects of SGLT2 inhibitor ipragliflozin in type 2 diabetic mice fed sugar solution. Eur J Pharmacol 2018; 818: 545-53.
[http://dx.doi.org/10.1016/j.ejphar.2017.11.020] [PMID: 29154936]
[114]
Fonseca VA, Ferrannini E, Wilding JP, et al. Active- and placebo- controlled dose-finding study to assess the efficacy, safety, and tolerability of multiple doses of ipragliflozin in patients with type 2 diabetes mellitus. J Diabetes Complications 2013; 27(3): 268-73.
[http://dx.doi.org/10.1016/j.jdiacomp.2012.11.005] [PMID: 23276620]
[115]
Kashiwagi A, Kazuta K, Yoshida S, Nagase I. Randomized, placebo-controlled, double-blind glycemic control trial of novel sodium-dependent glucose cotransporter 2 inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus. J Diabetes Investig 2014; 5(4): 382-91.
[http://dx.doi.org/10.1111/jdi.12156] [PMID: 25411597]
[116]
Poole RM, Prossler JE. Tofogliflozin: first global approval. Drugs 2014; 74(8): 939-44.
[http://dx.doi.org/10.1007/s40265-014-0229-1] [PMID: 24848755]
[117]
Nagata T, Fukazawa M, Honda K, et al. Selective SGLT2 inhibition by tofogliflozin reduces renal glucose reabsorption under hyperglycemic but not under hypo- or euglycemic conditions in rats. Am J Physiol Endocrinol Metab 2013; 304(4): E414-23.
[http://dx.doi.org/10.1152/ajpendo.00545.2012] [PMID: 23249697]
[118]
Kasahara-Ito N, Fukase H, Ogama Y, et al. Pharmacokinetics and pharmacodynamics of tofogliflozin (a selective SGLT2 inhibitor) in healthy male subjects. Drug Res (Stuttg) 2017; 67(6): 349-57.
[http://dx.doi.org/10.1055/s-0043-104779] [PMID: 28427104]
[119]
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(17): 7828-40.
[http://dx.doi.org/10.1021/jm300884k] [PMID: 22889351]
[120]
Schwab D, Portron A, Backholer Z, Lausecker B, Kawashima K. A novel double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]tofogliflozin after oral administration and concomitant intravenous microdose administration of [13C]tofogliflozin in humans. Clin Pharmacokinet 2013; 52(6): 463-73.
[http://dx.doi.org/10.1007/s40262-013-0051-z] [PMID: 23494983]
[121]
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(3): 692-701.
[http://dx.doi.org/10.1124/jpet.112.191593] [PMID: 22410641]
[122]
Lapuerta P, Zambrowicz B, Strumph P, Sands A. Development of sotagliflozin, a dual sodium-dependent glucose transporter 1/2 inhibitor. Expert Rev Endocrinol Metab 2015; 12(2): 101-10.
[http://dx.doi.org/10.1177/1479164114563304] [PMID: 25690134]
[123]
Rendell MS. Sotagliflozin: a combined SGLT1/SGLT2 inhibitor to treat diabetes. Expert Rev Endocrinol Metab 2018; 13(6): 333-9.
[http://dx.doi.org/10.1080/17446651.2018.1537779] [PMID: 30379091]
[124]
Yan PK, Zhang LN, Feng Y, et al. SHR3824, a novel selective inhibitor of renal sodium glucose cotransporter 2, exhibits antidiabetic efficacy in rodent models. Acta Pharmacol Sin 2014; 35(5): 613-24.
[http://dx.doi.org/10.1038/aps.2013.196] [PMID: 24786232]
[125]
NewDrugApproval Henagliflozin. 2016. Available from: https://newdrugapprovals.org/2016/04/16/henagliflozin/(16 April 2016)
[126]
DrugBank Bexagliflozin. 2020. Available from: https://www.drugbank.ca/drugs/DB12236(March 01, 2020)
[127]
Zhang W, Welihinda A, Mechanic J, et al. EGT1442, a potent and selective SGLT2 inhibitor, attenuates blood glucose and HbA(1c) levels in db/db mice and prolongs the survival of stroke-prone rats. Pharmacol Res 2011; 63(4): 284-93.
[http://dx.doi.org/10.1016/j.phrs.2011.01.001] [PMID: 21215314]
[128]
Halvorsen YC, Walford GA, Massaro J, Aftring RP, Freeman MW. A 96-week, multinational, randomized, double-blind, parallel-group, clinical trial evaluating the safety and effectiveness of bexagliflozin as a monotherapy for adults with type 2 diabetes. Diabetes Obes Metab 2019; 21(11): 2496-504.
[http://dx.doi.org/10.1111/dom.13833] [PMID: 31297965]
[129]
Allegretti AS, Zhang W, Zhou W, et al. Safety and effectiveness of bexagliflozin in patients with type 2 diabetes mellitus and stage 3a/3b CKD. Am J Kidney Dis 2019; 74(3): 328-37.
[http://dx.doi.org/10.1053/j.ajkd.2019.03.417] [PMID: 31101403]
[130]
Song L, Liu Y, Yao X, et al. Development of an HPLC-MS/MS method to determine janagliflozin in human plasma and urine: application in clinical study. Bioanalysis 2018; 10(17): 1439-54.
[http://dx.doi.org/10.4155/bio-2018-0129] [PMID: 30182735]
[131]
ClinicalTrials.gov Janagliflozin Treat T2DM Monotherapy. 2019. Available from: https://clinicaltrials.gov/ct2/show/record/NCT03811548?term=NCT03811548&draw=2&rank=1&view=record(22 January 2019)
[132]
Song L, Yao X, Liu Y, et al. Translational prediction of first-in-human pharmacokinetics and pharmacodynamics of janagliflozin, a selective SGLT2 inhibitor, using allometric scaling, dedrick and PK/PD modeling methods. Eur J Pharm Sci 2020; 147: 105281.
[http://dx.doi.org/10.1016/j.ejps.2020.105281] [PMID: 32126254]
[133]
NewDrugApproval Tianagliflozin IND filed by Tianjin Institute of Pharmaceutical research. 2016. Available from: https://newdrugapprovals.org/2016/03/30/tianagliflozin-ind-filed-by-tianjin-institute-of-pharmaceutical-research/(30.March.2016)
[134]
Zhang L, Wang Y, Xu H, et al. Discovery of 6-deoxydapagliflozin as a highly potent sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. Med Chem 2014; 10(3): 304-17.
[http://dx.doi.org/10.2174/15734064113096660051] [PMID: 24059684]
[135]
Bays HE, Kozlovski P, Shao Q, Proot P, Keefe D. Licogliflozin, a Novel SGLT1 and 2 Inhibitor: Body weight effects in a randomized trial in adults with overweight or obesity. Obesity (Silver Spring) 2020; 28(5): 870-81.
[http://dx.doi.org/10.1002/oby.22764] [PMID: 32187881]
[136]
He Y, Haynes WG, Meyers CD, et al. LIK066, a dual SGLT1/2 inhibitor, reduces weight and improves multipleincretin hormones in clinical proof-of-concept studies in obese patients with or without diabetes. Am Diabetes Assoc2018; 67(1).
[http://dx.doi.org/10.2337/db18-114-LB]
[137]
de Boer RA, Núñez J, Kozlovski P, Wang Y, Proot P, Keefe D. Effects of the dual sodium-glucose linked transporter inhibitor, licogliflozin vs. placebo or empagliflozin in patients with type 2 diabetes and heart failure. Br J Clin Pharmacol 2020; 86(7): 1346-56.
[http://dx.doi.org/10.1111/bcp.14248] [PMID: 32068914]
[138]
ClinicalTrials.gov A dose finding study to assess the effect of LIK066 compared to placebo or empagliflozin in patients With type 2 diabetes mellitus and heart failure. 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT03152552(August 28, 2019)
[139]
Lv B, Xu B, Feng Y, et al. Exploration of O-spiroketal C-arylglucosides as novel and selective renal sodium-dependent glucose co- transporter 2 (SGLT2) inhibitors. Bioorg Med Chem Lett 2009; 19(24): 6877-81.
[http://dx.doi.org/10.1016/j.bmcl.2009.10.088] [PMID: 19896374]
[140]
Xu B, Lv B, Feng Y, et al. O-Spiro C-aryl glucosides as novel sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors. Bioorg Med Chem Lett 2009; 19(19): 5632-5.
[http://dx.doi.org/10.1016/j.bmcl.2009.08.030] [PMID: 19700318]
[141]
Zhang X, Urbanski M, Patel M, et al. Heteroaryl-O-glucosides as novel sodium glucose co-transporter 2 inhibitors. Part 1. Bioorg Med Chem Lett 2005; 15(23): 5202-6.
[http://dx.doi.org/10.1016/j.bmcl.2005.08.067] [PMID: 16198559]
[142]
Dudash J Jr, Zhang X, Zeck RE, et al. Glycosylated dihydrochalcones as potent and selective sodium glucose co-transporter 2 (SGLT2) inhibitors. Bioorg Med Chem Lett 2004; 14(20): 5121-5.
[http://dx.doi.org/10.1016/j.bmcl.2004.07.082] [PMID: 15380212]
[143]
Lee SH, Kim MJ, Lee SH, Kim J, Park HJ, Lee J. Thiazolylmethyl ortho-substituted phenyl glucoside library as novel C-aryl glucoside SGLT2 inhibitors. Eur J Med Chem 2011; 46(7): 2662-75.
[http://dx.doi.org/10.1016/j.ejmech.2011.03.052] [PMID: 21514014]
[144]
Song KS, Lee SH, Kim MJ, et al. Synthesis and SAR of Thiazolylmethylphenyl Glucoside as Novel C-Aryl Glucoside SGLT2 Inhibitors. ACS Med Chem Lett 2010; 2(2): 182-7.
[http://dx.doi.org/10.1021/ml100256c] [PMID: 24900297]
[145]
Park EJ, Kong Y, Lee JS, Lee SH, Lee J. Exploration of SAR regarding glucose moiety in novel C-aryl glucoside inhibitors of SGLT2. Bioorg Med Chem Lett 2011; 21(2): 742-6.
[http://dx.doi.org/10.1016/j.bmcl.2010.11.115] [PMID: 21193308]
[146]
Zhou H, Danger DP, Dock ST, et al. Synthesis and SAR of Benzisothiazole- and Indolizine-β-d-glucopyranoside Inhibitors of SGLT2. ACS Med Chem Lett 2010; 1(1): 19-23.
[http://dx.doi.org/10.1021/ml900010b] [PMID: 24900169]
[147]
Chu KF, Yao CH, Song JS, et al. N-Indolylglycosides bearing modifications at the glucose C6-position as sodium-dependent glucose co-transporter 2 inhibitors. Bioorg Med Chem 2016; 24(10): 2242-50.
[http://dx.doi.org/10.1016/j.bmc.2016.03.058] [PMID: 27075813]
[148]
Jesus AR, Vila-Viçosa D, Machuqueiro M, Marques AP, Dore TM, Rauter AP. Targeting type 2 diabetes with c-glucosyl gihydrochalcones as selective sodium glucose co-transporter 2 (SGLT2) inhibitors: Synthesis and biological evaluation. J Med Chem 2017; 60(2): 568-79.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01134] [PMID: 28098449]
[149]
Guo C, Hu M, DeOrazio RJ, et al. The design and synthesis of novel SGLT2 inhibitors: C-glycosides with benzyltriazolopyridinone and phenylhydantoin as the aglycone moieties. Bioorg Med Chem 2014; 22(13): 3414-22.
[http://dx.doi.org/10.1016/j.bmc.2014.04.036] [PMID: 24842618]
[150]
Ding Y, Mao L, Xu D, et al. C-Aryl glucoside SGLT2 inhibitors containing a biphenyl motif as potential anti-diabetic agents. Bioorg Med Chem Lett 2015; 25(14): 2744-8.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.040] [PMID: 26026363]
[151]
Li Y, Shi Z, Chen L, et al. Discovery of a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor (HSK0935) for the treatment of type 2 diabetes. J Med Chem 2017; 60(10): 4173-84.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01818] [PMID: 28447791]
[152]
Yuan MC, Yeh TK, Chen CT, et al. Identification of an oxime- containing C-glucosylarene as a potential inhibitor of sodium-dependent glucose co-transporter 2. Eur J Med Chem 2018; 143: 611-20.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.019] [PMID: 29216560]
[153]
Kuo G-H, Gaul MD, Liang Y, et al. Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors. Bioorg Med Chem Lett 2018; 28(7): 1182-7.
[http://dx.doi.org/10.1016/j.bmcl.2018.02.057] [PMID: 29523385]
[154]
Lin TS, Liw YW, Song JS, et al. Synthesis and biological evaluation of novel C-aryl d-glucofuranosides as sodium-dependent glucose co-transporter 2 inhibitors. Bioorg Med Chem 2013; 21(21): 6282-91.
[http://dx.doi.org/10.1016/j.bmc.2013.08.067] [PMID: 24071445]
[155]
Yao CH, Song JS, Chen CT, et al. Synthesis and biological evaluation of novel C-indolylxylosides as sodium-dependent glucose co- transporter 2 inhibitors. Eur J Med Chem 2012; 55: 32-8.
[http://dx.doi.org/10.1016/j.ejmech.2012.06.053] [PMID: 22818040]
[156]
Goodwin NC, Mabon R, Harrison BA, et al. Novel L-xylose derivatives as selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes. J Med Chem 2009; 52(20): 6201-4.
[http://dx.doi.org/10.1021/jm900951n] [PMID: 19785435]
[157]
Yao CH, Song JS, Chen CT, et al. Discovery of novel N-β-D-xylosylindole derivatives as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the management of hyperglycemia in diabetes. J Med Chem 2011; 54(1): 166-78.
[http://dx.doi.org/10.1021/jm101072y] [PMID: 21128592]
[158]
Pittampalli S, Upadyayula S, Mekala HM, Lippmann S. Risks vs. benefits for sglt2 inhibitor medications. Fed Pract 2018; 35(7): 45-8.
[PMID: 30766374]
[159]
Clar C, Gill JA, Court R, Waugh N. Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. BMJ Open 2012; 2(5): e001007.
[http://dx.doi.org/10.1136/bmjopen-2012-001007] [PMID: 23087012]
[160]
Singh M, Kumar A. Risks associated with SGLT2 inhibitors: an overview. Curr Drug Saf 2018; 13(2): 84-91.
[http://dx.doi.org/10.2174/1574886313666180226103408] [PMID: 29485006]
[161]
Taylor SI, Blau JE, Rother KI. SGLT2 inhibitors may predispose to ketoacidosis. J Clin Endocrinol Metab 2015; 100(8): 2849-52.
[http://dx.doi.org/10.1210/jc.2015-1884] [PMID: 26086329]
[162]
Westcott GP, Segal AR, Mitri J, Brown FM. Prolonged glucosuria and relapse of diabetic ketoacidosis related to SGLT2-inhibitor therapy. Endocrinol Diabetes Metab 2020; 3(2): e00117.
[http://dx.doi.org/10.1002/edm2.117] [PMID: 32318635]
[163]
Mayer P. Chances and risks of SGLT2 inhibitors. Naunyn Schmiedebergs Arch Pharmacol 2012; 385(6): 551-4.
[http://dx.doi.org/10.1007/s00210-011-0720-0] [PMID: 22198467]
[164]
Fala L. Jardiance (empagliflozin), an sglt2 inhibitor, receives fda approval for the treatment of patients with type 2 diabetes. Am Health Drug Benefits 2015; 8(Spec Feature): 92-5.
[165]
Kashiwagi A, Takahashi H, Ishikawa H, et al. A randomized, double-blind, placebo-controlled study on long-term efficacy and safety of ipragliflozin treatment in patients with type 2 diabetes mellitus and renal impairment: Results of the long-term ASP1941 safety evaluation in patients with type 2 diabetes with renal impairment (LANTERN) study. Diabetes Obes Metab 2015; 17(2): 152-60.
[http://dx.doi.org/10.1111/dom.12403] [PMID: 25347938]

Rights & Permissions Print Cite
Article Metrics
19
1
© 2024 Bentham Science Publishers | Privacy Policy