SGLT2 Inhibitors: A New Generation of Antidiabetic Drugs
DOI:
https://doi.org/10.37285/ijpsn.2015.8.2.1Abstract
The incidence of type 2 diabetes is markedly increasing worldwide. Despite a plethora of therapeutic options available for the treatment of type 2 diabetes, the ability to effectively normalize blood glucose levels and prevent long-term complications of diabetes remains elusive. There is intense search for new drugs for diabetes. One novel therapeutic class of antidiabetic drugs is sodium-glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 is renal membrane transporter that plays an important role in glucose reabsorption within kidneys. Hence, inhibition of SGLT2 enhances renal glucose excretion, consequently lowers blood glucose levels in an insulin- independent manner. This article describes various SGLT2 inhibitors currently available in the market and also agents that are undergoing clinical trials for the treatment of type 2 diabetes. Currently three SGLT2 inhibitors are approved for clinical use and several others are still in development. The emerging data suggest that SGLT2 inhibitors hold great promise for the clinical management of type 2 diabetes. It remains to be seen whether this class of drugs offers additional advantages over the existing oral hypoglycemic agents.
Downloads
Metrics
Keywords:
Dapagliflozin, Canagliflozin, Empagliflozin, SGLT2, Kidney, Diabetes, Blood glucose
Downloads
Published
How to Cite
Issue
Section
References
Abdul Ghani MA and DeFronzo RA. Inhibition of Renal Glucose Reabsorption: A Novel Strategy for Achieving Glucose Control in Type 2 Diabetes Mellitus. Endocrpract. 14: 782-790.
Anjana Rm, Ali Mk, Pradeepa R, Datta M, Unnikrishnan R, Rema M and Mohan V (2011). The Need for Obtaining Accurate Nationwide Estimates of Diabetes Prevalence in India – Rationale for A National Study on Diabetes. Indian J Med Res 133(4): 369-380.
Bakris GL, Fonseca VA, Sharma K and Wright EM (2009). Renal Sodium Glucose Transport: Role in Diabetes Mellitus and Potential Clinical Implications. Kidney Int. 75: 1272-1277.
Bhartia M, Tahrani AA and Barnett AH (2011). SGLT2 Inibitors in Development for Type 2 Diabetes Treatment. Rev Diabet Stud. 8(3): 348-354.
Boldys A and Okopieri B (2009). Inhibitors of Type 2 Sodium Glucose Co-Transporter-A New Strategy for Diabetes Treatment. Pharmacological Report. 61: 778-784.
Bowles P, Brenek SJ, Caron S, DoNM, Drexler MT, Duan S, Dube P, Hansen EC, Jones BP, Jones KN, Ljubicic TA, Makowski TW, Mustakis J, Nelson JD, Olivier M, Peng Z, Perfect HH, Place DW, Ragan JA, Salisbury JJ, Stanchina CL, Vanderplas BC, Webster ME and Matt Weekly R (2014). Commercial Route Research and Development for SGL2 Inhibitor Candidate Ertugliflozin.Org Process Res Dev. 18(1): 66-81.
Chao EC and Henry RR (2010). SGLT2 Inhibition - A Novel Strategy for Diabetes Treatment. Nature. Reviews Drug Discovery. 9(7): 551-559.
Clarke T (2013). FDA approves Johnson and Johnson Diabetes Drug, Canagliflozin. Reuterswww.reuters.com/article/2013/03/29/us-usa-johnsonandjohnson-diabetes-idUSBRE92S0EY20130329
Control G, Turnbull FM, Abraura C, Anderson RJ, Byington RP, Chalmers JP, Duckworth WC, Evans GW, Gerstein HC, Holman RR, Moritz TE, Neal BC, Ninomiya T, Patel AA, Paul SK, Travert F and Woodward M (2009). Intensive Glucose Control and Macrovascular Outcomes in Type 2 Diabetes. Diabetologia 52(11): 2288-2298.
Deepa M, Bhansali A, Anjana RM, Pradeepa R, Joshi SR, Joshi PP, Dhandhania VK, Rao PV, Subashini R, Unnikrishnan R, Shukla DK, Madhu SV, Das AK, Mohan V and Kaur T (2014). Knowledge and Awareness of Diabetes in Urban and Rural India: The Indian Council of Medical Research India Diabetes Study (Phase I): Indian Council of Medical Research India Diabetes 4. Indian J Endocrinol Metab. 18(3): 379-385.
DeFronzo Rand Banting Lecture (2009). From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus. Diabetes 58: 773-795.
DeFronzo RA, Davidson JA and Del Prato S (2012). The role of the Kidneys in Glucose Homeostasis: A New Path towards Normalizing Glycaemia. Diabetes Obes Metab. 14(1): 5-14.
Devineni D, Morrow L, Hompesch M, Skee D, Vandebosch A, Murphy J Ways K and Schwartz S (2012). Canagliflozin Improves Glycaemic Control over 28 Days in Subjects with Type 2 Diabetes not Optimally Controlled on Insulin..Diabetes Obes Metab.14: 539-545.
Dobbins RL, O’Connor-Semmes R, Kapur A, Kapitza C, Golor G, Mikoshiba I Tao W and Hussey EK (2012). Remogliflozinetabonate, A Selective Inhibitor of The Sodium-Dependent Transporter 2 Reduces Serum Glucose in Type 2 Diabetes Mellitus Patients. Diabetes Obes Metab. 14(1): 15-22.
Elizabeth Mechatie for Clinical Endocrinology News Digital Network August 1, 2014 FDA approves Empagliflozin for Adults with Type 2 Diabetes
Farber SJ, Berger EY and Earle DP (1951). Effect Of Diabetes and Insulin of the Maximum Capacity of The Renal Tubules to Reabsorb Glucose. J Clin Invest 30: 125-129.
Ferrannini E, Ramos SJ, Salsali A, Tang W and List JF (2010). Dapagliflozin Monotherapy in Type 2 Diabetic Patients with Inadequate Glycemic Control by Diet and Exercise: A Randomizex, Double-Blind, Placebo-Controlled, Phase III Trial. Diabetes Care. 33(10): 2217-2224.
Fonseca VA, Ferrannini E, Wilding JP, Whilpshar W, Dhanjal P, Ball G and Klasen S (2013). 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. 27, 268-273.
Fujimori Y, Katsuno K, Nakashima I, Ishikawa-Takemura Y, Fujikura H and Isaji M (2008). Remogliflozinetabonate, in a Novel Category of Selective Low-Affinity Sodium Glucose Cotransporter (SGLT2) Inhibitors, Exhibits Antidiabetic Efficacy in Rodent Models. J Pharmacol Exp Ther. 327(1): 268-276.
Fujimori Y, Katsuno K, Ojima K, Nakashima I, Nakano S, Ishikawa-Takemura Y, Kusama H and Isaji M (2009). Sergliflozinetabonate, A Selective SGLT2 Inhibitor, Improves Glycemic Control in Steptozotocin-Induced Diabetic Rats and Zucker Fatty Rats. Eur J Pharmacol . 609: 148-154.
Grempler R, Thomas L, Eckhardt M, Himmelsbach F, Sauer A, Sharp DE, Bakker RA, Mark M, Klein T and Eickelmann P (2012). Empagliflozin, A Novel Selective Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitor: Characterisation and Comparison with other SGLT-2 inhibitors.Diabetes Obes Metab.14(1): 83-90.
Han S, Hagan S, Hagan DL and Taylor JR (2008). Dapagliflozin, a Selective SGLT2 Inhibitor, Improves Glucose Homeostasis in Normal and Diabetic Rats. Diabetes. 57: 1723-1729.
Heise T, Seman L, Macha S, Jones P, Marquart A, Pinnetti S, Woerle HJ and Dugi K (2013a). Safety, Tolerability, Pharmacokinetic, and Pharmacodynamics of Multiple Raising Doses of Empagliflozin in Patients with Type 2 Diabetes Mellitus. Diabetes Ther Epub. 4(2): 331-345.
Heise T, Seewaldt-Becker E, Macha S, Hantel S, Pinnetti S, Seman L and Woerle HJ (2013b). Safety, Tolerability, Pharmacokinetic, and Pharmacodynamics Following 4 Weeks Treatment with Empagliflozin once Daily in Patients with Type 2 Diabetes Mellitus. Diabetes Obes Metab . 15(7): 613-621.
Hussey, EK, Clark RV, Amin DM, Kipnes MS, O’Connor-Semmes RL, O’Driscoll EC, Leong J, Murray SC, Dobbins RL, Layko D and Nunez DJR (2010a). Single-Dose Pharmacokinetics and Pharmacodynamics of Sergliflozinetabonate, A Novel Inhibitor of Glucose Reabsorption, in Healthy Volunteers and Patients with Type 2 Diabetes Mellitus. J ClinPharmacol. 50(6): 623-635.
Hussey EK, Dobbins RL, Stoltz RR, Stockman NL, O’Connor-Semmes RL, Kapur A, Murray SC, Layko D and Nunez DJR (2010b). Multiple-Dose Pharmacokinetics and Pharmaco-Dynamics of Sergliflozinetabonate, A Novel Inhibitor of Glucose Reabsorption, in Healthy Overweight and Obese Subjects: A Randomized Double-Blind Study. J ClinPharmacol. 50(6): 636-646.
Hussey E, Clark RV and Amin DM (2007). Early Clinical Studies to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of Sergliflozin, A Novel Inhibitor or Renal Glucose Reabsorption in Healthy Volunteers and Subjects with Type 2 Diabetes Mellitus. Diabetes. 56:A49.
Imamura M, Kasai M, Komenoi K, Nakamura A, Nakanishi K and Shiraki R (2009). Method for Producing C-Glycoside Derivative and Synthetic Intermediate Thereof. EP 2105442 A1.
Imamura M, Nakanishi K, Suzuki T, Ikegai K, Shiraki R and Ogiyama T (2012). Discovery of Ipragliflozin (ASP 1941): A Novel C-Glucoside with Benzothiophene Structure as Potent and Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes Mellitus. Bioorg Med Chem. 20(10): 3263-3279.
International Diabetes Federation: IDF Diabetes Atlas, 6th edition, Brussels, Belgium, 2013.
Iyobe A, Teranishi H, Tatani K, Yonikubo S and Isaji M (2004). Crystals of Glucopyranosyloxybenyl Benzene Derivative. Europ Patent. 1489 089A1
Janssen Pharmaceuticals, Inc. (2013). FDA Advisory Committee Meeting. FDA briefingdocument. NDA 204042. (canagliflozin)
John R and White Jr PA (2010). Apple Trees to Sodium Glucose Co-Transporter Inhibitors: A Review of SGLT2 Inhibition. Clinical Diabetes. 28(1): 5-10.
Kadokura T, Zhang W, Krauwinkel W Leeflang S, Keirns J, Taniuchi Y, Nakajo I and Smulders R (2014). Clinical Pharmacokinetics and Pharmacodynamics of the Novel SGLT2 Inhibitor Ipragliflozin. Clin Pharmacokinet. 53(11): 975-988.
Kaku K, Watada H, Iwamoto Y, Utsunomiya K,Terauchi Y, Tobe K, Tanizawa Y, Araki E, Ueda M, Suganami H, Watanabe D and Tofogliflozin 003 Study Group (2014). Efficacy and Safety of Monotherapy with the Novel Sodium/Glucose Cotransporter-2 Inhibitor Tofogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Combined Phase 2 and 3 Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Comparative Study. Cardiovasc Diabetol. 13: 65.
Kalgutkar AS, Tugnait M, Zhu T, Kimoto E, Miao Z, Mascitti V, Yang X, Tan B, Walsky RL, Chupka J, Feng B and Robinson RP (2011). Preclinical Species and Human Disposition of Pf-04971729, A Selective Inhibitor of the Sodium-Dependent Glucose Cotransporter 2 and Clinical Candidate for the Treatment of Type 2 Diabetes Mellitus. Drug Metab Dispos. 39(9): 1609-1619.
Kapur A, O’Connor-Semmes R, Hussey EK, Dobbin RL, Tao W and Hompesch M (2013). First Human Dose-Escalation Study with Remogliflozinetabonate, A Selective Inhibitor of the Sodium-Glucose Transporter 2 (SGLT2), in Healthy Subjects and in Subjects with Type 2 Diabetes Mellitus. BMC Pharmacol Toxicol. 14: 26.
Kashiwagi A, Kazuta K, Takinami Y, Yoshida S, Utsuno A and Nagase I (2014). Ipragliflozin Improves Glycemic Control in Japanese Patients with Type 2 Diabetes Mellitus: The Brighten Study. Diabetol Int. 6(1): 8-18.
Katsuno K, Fujimori Y, Takemura Y, Hiratochi M, Itoh F, Komatsu Y, Fujikura H and Isaji M (2007). 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 . 320: 323-330.
Katsuno K, Fujimori Y, Ishikawa-Takemura Y and Isaji M (2009). Long-Term Treatment with Sergliflozinetabonate Improves Disturbed Glucose Metabolism.in Kk-A (Y) Mice. Eur J Pharmacol . 618: 98-104.
Kaveeshwar SA and Cornwall J. The current State of Diabetes Mellitus in India. Australas Med J 7(1): 45-48.
Komoroski B, Vachharajani N, Feng Y and Pfister M (2009). Dapagliflozin, A Novel, Selective SGLT2 Inhibitor, Improved Glycemic Control over 2 Weeks in Patients with Type 2 Diabetes Mellitus. Clin Pharmacol Ther. 85: 513-519.
Lee WS, Wells RG and Hediger MA (1994). The High Affinity Na/Glucose Cotransporter: Reevaluation and Distribution of Expression. J Biol Chem. 269: 12032-12039.
List JF, Woo V, Morales E, Tang W and Fiedorek FT (2009). Sodium-Glucose Cotransport Inhibition with Dapagliflozin in Type 2 Diabetes. Diabetes Care. 32: 650-657.
Mascitti V and Collman BM (2010). Preparation of Dioxa-Bicyclo[3.2.1]Octane-2,3,4-Triol Derivatives as Anti-Diabetic Agents. PTC Int Appli WO 2010023594; chemabstr. 152: 311862.
Mascitti V, Maurer TS, Robinson RP, Bian J, Boustany-Kari CM, Brandt T, Collman BM, Kalgutkar AS, Klenotic MK, Leininger MT, Lowe A, Maguere RJ, Masterson VM, Miao Z, Mukaiyama E, Patel JD, Pettersen JC, Preville C, Samas B, She L, Sobol Z, Steppan CM, Stevens BD,Thuma BA, Tugnait M, Zeng D and Zhu T (2011). 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 54(8): 2952-2960.
Meng W, Ellsworth BA and Nirschl AA (2008). Discovery of Dapagliflozin: A Potent Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes.J Med Chem. 51: 1145-1149.
Miao Z, Nucci G, Amin N, Sharma R, Mascitti V, Tugnait M, Vaz AD, Callegari E and Kalgutkar AS (2013). Pharmacokinetics, Metabolism and Excretion of the Antidiabetic Agent Ertugliflozin (Pf-04971729) in Healthy Male Subjects. Drug MetabDispos. 41(2): 445-456.
Miriam, E. Tucker for Medscape Medical News. May 07, 2013 First Details of Empagliflozin Trials Follow US and EU Filings
Mohan V, Sandeep S, Deepa R, Shah B and Varghese C (2007). Epidemiology of Type 2 Diabetes: Indian Scenario. Indian J Med Res. 125: 217-230.
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Homan RR, Sherwin R and Zinman B (2006). Management of Hyperglycaemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy. A Consensus Statement from American Diabetes Association and the Europe Association for the Study of Diabetes. Diabetologia. 49: 1711-1721.
Nomura S, Sakamaki S, Hongu M, Kawanishi E, Koga Y, Sakamoto T, Yamamoto Y Ueta K, Kimata H, Nakayama K and Tsuda-Tsukimoto M (2010). Discovery of Canagliflozin, A Novel C-Glycoside with Thiophene Ring, as Sodium-Dependent Cotransporter 2 Inhibitor for the Treatment of Type 2 Diabetes Mellitus. J Med Chem. 53(17): 6355-6360.
Nyirjesy P, Zhao Y, Ways K and Usiskin K (2012). Evaluation of Vulvovaginal Symptoms and Candida Colonization in Women with Type 2 Diabetes Mellitus Treated with Canagliflozin, A Sodium Glucose Co-Transporter 2 Inhibitor. Curr Med Res Opin. 28(7): 1173-1178.
Ohtake Y, Sato T, Kobayashi T, Nishimoto M, Taka N, Takano K, Yamamoto K, Ohmori M, Yamaguchi M, Takami K, YeuS Y, Ahn KH, Matsuoka H, Morikawa K, Suzuki M, Hagita H, Ozawa K, Yamaguchi K, Kato M and Ikeda S (2012). 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. 55(17): 7828-7840.
Oku A, Ueta K, Arakawa K, Ishihara T, Nawano M, Kuronuma Y, Matsumoto M, Saito A, Tsujihara K, Anaj M, Asano T Kanai Y and Endou H (1999). T-1095, An Inhibitor of Renal Na+-Glucose Cotransporters, May Provide A Novel Approach to Treating Diabetes. Diabetes. 48: 1794-1800.
Oliveros RA, Son V, Bailey SR and Chilton RJ (2014). Glucose Control and Cardiovascular Outcomes in Clinical Trials of Sodium Glucose Co-Transporter 2 Inhibitor Treatments in Type 2 Diabetes. US Endocrynology . 10(1): 8-15.
Poole RM and Dungo RT (2014a). Ipragliflozin: First Global Approval. Drugs. 74(5): 611-617.
Poole RM and Prossler JE (2014b). Tofogliflozin: First Global Approval. Drugs. 74(8): 939-944.
Poudel RR (2013). Renal Glucose Handling in Diabetes and Sodium Glucose Cotransporter 2 Inhibition. Indian J Endocrinol Metab. 17(4): 588-593.
Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G and Brown J (2005). Glucose Transporters in Human Renal Proximal Tubular Cells Isolated from the Urine Of Patients with Non-Insulin Dependent Diabetes. Diabetes. 54: 3427-3434.
Roden M, Weng J, Eilbracht J, Delafont B, Kim G, Woerle JH, Broedl CU and EMPA-REG Mono Trial Investigators (2013). Empagliflozin Monotherapy with Sitagliptin as an Active Comparator in Patients with Type 2 Diabetes: A Randomized Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet Diabetes Endocrinol. 1(3): 208-219.
Riser TS and Harris KB (2013). The Clinical Efficacy and Safety of Sodium Glucose Cotransporter-2 Inhibitors in Adults with Type 2 Diabetes Mellitus. Pharmacotherapy, 33(9): 984-999.
Rosenstock J, Aggarwal N, Polidori, D Zhao Y, Arbit D, Usiskin K, Capuano G, Canovatchel W; Canagliflozin DIA 2001 Study Group (2012a). Dose-Ranging Effects of Canagliflozin, A Sodium-Glucose Cotransporter 2 Inhibitor, as Add-On to Metformin in Subjects with Type 2 Diabetes. Diabetes Care. 35: 1232-1238.
Rosenstock J, Vico M, Wei L, Salsali A, List FJ (2012b). Effects Of Dapagliflozin, an SGLT2 Inhibitor, on Hba1c, Bodyweight and Hypoglycemia Risk in Patients with Type 2 Diabetes Inadequately Controlled on Pioglitazone Monotherapy. Diabetes Care. 35(7): 1473-1478.
Rossetti L, Smith D, Shulman GI, Papachristou D and DeFronzo RA (1987). Correction Of Hyperglycemia with Phlorizin Normalizes Tissue Sensitivity to Insulin in Diabetic Rats. J Clin Invest. 79(5): 1510-1515.
Schwab D, Portron A, Backholer Z, Lausecker B and Kawashima K (2013). A Novel Double-Tracer Technique to Characterize Absorption, Distribution, Metabolism and Excretion (Adme) of [14c] Tofogliflozin after Oral Admistration and Concomitant Intravenous Microdose Administration of [13c] Tofogliflozin in Humans.Clin Pharmacokinet . 52(6): 463-473.
Shiohara H, Fujikura H, Fushimi N, Ito F and Isaji M (2007). Glucopyranosyloxypyrazole Derivative, Medicinal Composition Containing the Same, Medicinal Use Thereof, and Intermediate Therefor. Eur Patent. 1400529A4.
Stenlof K, Cefalu WT, Kim KA, Alba M, Usiskin K, Tong C, Canovatchel W and Meininger G (2013). Efficacy and Safety of Canagliflozin Monotherapy in Subjects with Type 2 Diabetes Mellitus Inadequately Controlled with Diet and Exercise. Diabetes Obes Metab . 15: 372-382.
Suzuki M, Honda K, Fukazawa M, Ozawa K,Hagita H, Kawai T, Takeda M, Yata T, Kawai M, Fukuzawa T, Kobayashi T, Sato T, Kawabe Y and Ikeda S (2012). Tofogliflozin, a Potent and Highly Specific Sodium/Glucose Cotransporter 2 Inhibitor, Improves Glycemic Control in Diabetic Rats and Mice. J Pharmacol Exp Ther. 341: 692-701.
Tang C and Zhu X (2012). A Specific Pharmacophore Model of Sodium Dependent Glucose Co-Transporter 2 (SGLT2) Inhibitors. J Mol Model . 18: 2795-2804.
Tatoń J, Piatkiewicz P and Czech A (2010). Molecular Physiology of Cellular Glucose Transport- A Potential Area for Clinical Studies in Diabetes Mellitus. Endokrynol Pol . 61(3): 303-310.
Tharkar S, Devarajan A, Kumpatla S and Viswanathan V (2010). The Socioeconomics of Diabetes from A Developing Country: A Population Based Cost of illness Study. Diabetes Res Clin Pract. 89(3): 334-340.
Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, Sarigianni M, Matthews DR and Tsapas A (2013). Sodium-Glucose Cotranspoter 2 Inhibitors for Type 2 Diabetes: A Systematic Review and Meta-Analysis. Ann Intern Med. 159(4): 262-274.
Venkataraman K, Kannan AT and Mohan V (2009). Challenges in Diabetes Management with Particular Reference to India. Int J Diabetes Dev Ctries. 29(3): 103-109.
Vick H, Diedrich DF and Baumman K (1973). Reevaluation of Renal Tubular Glucose Transport Inhibition by Phlorizin Analogs. Am J Physiol . 224: 552-557.
Wang X, Zhang L, Byrne D, Nummy L, Weber D, Krishnamurthy D, Nathan Y and Senanayake CH (2014). Efficient Synthesis of Empagliflozin, an Inhibitor of SGLT2, Utilizing an Alcl3-Promoted Silane Reduction of A Β-Glycopyranoside. Org Lett. 16(16): 4090-4093.
Well RG, Mohandas TK and Hediger MA (1993). Localization of the Na+/Glucose Cotranspoter Gene SGLT2 to Human chromosome 16 Close to the Centromere. Genomics. 17(3): 787-789.
Wild S, Roglic G, Green A, Sicree R and King H. Global Prevalence of Diabetes – Estimates for the Year 2000 and Projections for 2030. Diabetic Care . 27: 1047-1053.
Willson MN and White Jr JR (2013). SGLT2 Inhibitors: A Review of Canagliflozin.US Pharm. 38(10): HS13-HS20.
Wright EM, Hirayama BA and Loo DF (2007). Active Sugar Transport in Health and Disease. J Inern Med. 261: 32-43.
Yale, J.F., Bakris, G., Cariou, B, Yue D, David-Neto E, Xi L, Figueroa K, Wajs E, Usiskin and Meininger G (2013). Efficacy and Safety of Canagliflozin in Subjects with Type 2 Diabetes and Chronic Kidney Disease. Diabetes ObesMetab. 15(5): 463-473.
Zell M, Husser C, Kuhlmann O, Schwab D, Uchimura T, Kemei T Kawashima K, Yamane M and Pahler A (2014). Metabolism and Mass Balance of SGLT2 Inhibitor Tofogliflozin Following Oral Administration to Humans. Xenobiotica. 44(4): 369-378.
