Development of the sodium-glucose co-transporter 2 inhibitor dapagliflozin for the treatment of patients with Type 2 diabetes mellitus

References

• American Diabetes Association. Standards of medical care in diabetes. Diabetes Care34(Suppl. 1), S11–S61 (2011).
   PubMed Web of Science ®Google Scholar
• Chan JL, Abrahamson MJ. Pharmacological management of Type 2 diabetes mellitus: rationale for rational use of insulin. Mayo Clin. Proc.78(4), 459–467 (2003).
   PubMed Web of Science ®Google Scholar
• Fowler M. Microvascular and macrovascular complications of diabetes. Clin. Diabetes26(2), 77–82 (2008).
   Google Scholar
• Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet. Med.27(2), 136–142 (2010).
   PubMed Web of Science ®Google Scholar
• Bakris GL, Fonseca VA, Sharma K, Wright EM. Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int.75(12), 1272–1277 (2009).
   PubMed Web of Science ®Google Scholar
• Gerich JE, Meyer C, Woerle HJ, Stumvoll M. Renal gluconeogenesis: its importance in human glucose homeostasis. Diabetes Care24(2), 382–391 (2001).
   PubMed Web of Science ®Google Scholar
• Owen OE, Felig P, Morgan AP, Wahren J, Cahill GF Jr. Liver and kidney metabolism during prolonged starvation. J. Clin. Invest.48(3), 574–583 (1969).
   PubMed Web of Science ®Google Scholar
• Bjorkman O, Felig P, Wahren J. The contrasting responses of splanchnic and renal glucose output to gluconeogenic substrates and to hypoglucagonemia in 60-h-fasted humans. Diabetes29(8), 610–616 (1980).
   Google Scholar
• Ekberg K, Landau BR, Wajngot A et al. Contributions by kidney and liver to glucose production in the postabsorptive state and after 60 h of fasting. Diabetes48(2), 292–298 (1999).
   PubMed Web of Science ®Google Scholar
• Meyer C, Dostou JM, Gerich JE. Role of the human kidney in glucose counterregulation. Diabetes48(5), 943–948 (1999).
   PubMed Web of Science ®Google Scholar
• Cersosimo E, Garlick P, Ferretti J. Renal glucose production during insulin-induced hypoglycemia in humans. Diabetes48(2), 261–266 (1999).
   PubMed Web of Science ®Google Scholar
• Ross BD, Espinal J, Silva P. Glucose metabolism in renal tubular function. Kidney Int.29(1), 54–67 (1986).
   PubMed Web of Science ®Google Scholar
• Meyer C, Dostou JM, Welle SL, Gerich JE. Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis. Am. J. Physiol. Endocrinol. Metab.282(2), E419–E427 (2002).
   PubMed Web of Science ®Google Scholar
• Hediger MA, Kanai Y, You G, Nussberger S. Mammalian ion-coupled solute transporters. J. Physiol.482(Suppl.), 7S–17S (1995).
   PubMed Web of Science ®Google Scholar
• 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.93(1), 397–404 (1994).
   PubMed Web of Science ®Google Scholar
• Bishop JH, Green R, Thomas S. Free-flow reabsorption of glucose, sodium, osmoles and water in rat proximal convoluted tubule. J. Physiol.288, 331–351 (1979).
   PubMed Web of Science ®Google Scholar
• Hediger MA, Rhoads DB. Molecular physiology of sodium-glucose cotransporters. Physiol. Rev.74(4), 993–1026 (1994).
   PubMed Web of Science ®Google Scholar
• Wright EM, Hirayama BA, Loo DF. Active sugar transport in health and disease. J. Intern. Med.261(1), 32–43 (2007).
   PubMed Web of Science ®Google Scholar
• Ferrannini E. Sodium-glucose transporter-2 inhibition as an antidiabetic therapy. Nephrol. Dial. Transplant.25(7), 2041–2043 (2010).
   PubMed Web of Science ®Google Scholar
• Meyer C, Stumvoll M, Nadkarni V, Dostou J, Mitrakou A, Gerich J. Abnormal renal and hepatic glucose metabolism in Type 2 diabetes mellitus. J. Clin. Invest.102(3), 619–624 (1998).
   PubMed Web of Science ®Google Scholar
• Meyer C, Woerle HJ, Dostou JM, Welle SL, Gerich JE. Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in Type 2 diabetes. Am. J. Physiol. Endocrinol. Metab.287(6), E1049–E1056 (2004).
   PubMedGoogle Scholar
• 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. Diabetes54(12), 3427–3434 (2005).
   PubMed Web of Science ®Google Scholar
• Santer R, Calado J. Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target. Clin. J. Am. Soc. Nephrol.5(1), 133–141 (2010).
   PubMed Web of Science ®Google Scholar
• Scholl-Burgi S, Santer R, Ehrich JH. Long-term outcome of renal glucosuria type 0: the original patient and his natural history. Nephrol. Dial. Transplant.19(9), 2394–2396 (2004).
   PubMed Web of Science ®Google Scholar
• Calado J, Loeffler J, Sakallioglu O et al. Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting. Kidney Int.69(5), 852–855 (2006).
   PubMed Web of Science ®Google Scholar
• Calado J, Sznajer Y, Metzger D et al. Twenty-one additional cases of familial renal glucosuria: absence of genetic heterogeneity, high prevalence of private mutations and further evidence of volume depletion. Nephrol. Dial. Transplant.23(12), 3874–3879 (2008).
   PubMed Web of Science ®Google Scholar
• Brown GK. Glucose transporters: structure, function and consequences of deficiency. J. Inherit. Metab. Dis.23(3), 237–246 (2000).
   PubMed Web of Science ®Google Scholar
• Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab. Res. Rev.21(1), 31–38 (2005).
   PubMed Web of Science ®Google Scholar
• Kahn BB, Shulman GI, DeFronzo RA, Cushman SW, Rossetti L. Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression. J. Clin. Invest.87(2), 561–570 (1991).
   PubMed Web of Science ®Google Scholar
• Rossetti L, Smith D, Shulman GI, Papachristou D, DeFronzo RA. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J. Clin. Invest.79(5), 1510–1515 (1987).
   PubMed Web of Science ®Google Scholar
• White JR. Apple trees to sodium glucose co-transporter inhibitors: a review of SGLT2 inhibition. Clin. Diabetes28(1), 5–10 (2010).
   Google Scholar
• Marsenic O. Glucose control by the kidney: an emerging target in diabetes. Am. J. Kidney Dis.53(5), 875–883 (2009).
   PubMed Web of Science ®Google Scholar
• Washburn WN. Development of the renal glucose reabsorption inhibitors: a new mechanism for the pharmacotherapy of diabetes mellitus Type 2. J. Med. Chem.52(7), 1785–1794 (2009).
   PubMed Web of Science ®Google Scholar
• Hoerger TJ, Segel JE, Gregg EW, Saaddine JB. Is glycemic control improving in US adults? Diabetes Care31(1), 81–86 (2008).
   PubMed Web of Science ®Google Scholar
• Cheung BM, Ong KL, Cherny SS, Sham PC, Tso AW, Lam KS. Diabetes prevalence and therapeutic target achievement in the United States, 1999 to 2006. Am. J. Med.122(5), 443–453 (2009).
   PubMed Web of Science ®Google Scholar
• Boyle JP, Thompson TJ, Gregg EW, Barker LE, Williamson DF. Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence. Popul. Health Metr.8(1), 29 (2010).
   PubMed Web of Science ®Google Scholar
• 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.327(1), 268–276 (2008).
   PubMed Web of Science ®Google Scholar
• Fujimori Y, Katsuno K, Ojima K et al. Sergliflozin etabonate, a selective SGLT2 inhibitor, improves glycemic control in streptozotocin-induced diabetic rats and Zucker fatty rats. Eur. J. Pharmacol.609(1–3), 148–154 (2009).
   PubMed Web of Science ®Google Scholar
• Dobbins RL, Kapur A, Kapitza C, O’Connor-Semmes RL, Tao W, Hussey EK. Remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2 (SGLT2) reduces serum glucose in Type 2 diabetes mellitus (T2DM) patients. Diabetes59(Suppl. 1), (2010) (Abstract 573-P).
   Google Scholar
• Hussey EK, Kapur A, O’Connor-Semmes RL, Tao W, Poo JL, Dobbins RL. Safety, pharmacokinetics and pharmacodynamics of remogliflozin etabonate (SGLT2 inhibitor) and metformin when co-administered in Type 2 diabetes mellitus (T2DM) patients. Diabetes59(Suppl. 1), (2010) (Abstract 564-P).
   Google Scholar
• Hussey EK, Clark RV, Amin DM et al. Single-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a novel inhibitor of glucose reabsorption, in healthy volunteers and patients with Type 2 diabetes mellitus. J. Clin. Pharmacol.50(6), 623–635 (2010).
   PubMed Web of Science ®Google Scholar
• Obermeier M, Yao M, Khanna A et al.In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans. Drug Metab. Dispos.38(3), 405–414 (2010).
   PubMed Web of Science ®Google Scholar
• Bellamine A, Smarsh M, Onorato J et al. Dapagliflozin (BMS-512148) is a competitive, selective and reversible inhibitor of human SGLT2. Presented at: Biomedical Transporters Conference. Thun, Switzerland, 9–13 August 2009.
   Google Scholar
• Han S, Hagan DL, Taylor JR et al. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes57(6), 1723–1729 (2008).
   PubMed Web of Science ®Google Scholar
• 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.51(5), 1145–1149 (2008).
   PubMed Web of Science ®Google Scholar
• Komoroski B, Vachharajani N, Boulton D et al. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin. Pharmacol. Ther.85(5), 520–526 (2009).
   PubMed Web of Science ®Google Scholar
• 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.85(5), 513–519 (2009).
   PubMed Web of Science ®Google Scholar
• Feng Y, Zhang L, Komoroski B, Pfister M. Population pharmacokinetic analysis of dapagliflozin in healthy and subjects with type 2 diabetes mellitus. Clin. Pharmacol. Ther.83(Suppl. 1), (2008) (Abstact s93).
   Google Scholar
• Kasichayanula S, Liu X, Shyu WC et al. Lack of pharmacokinetic interaction between dapagliflozin, a novel sodium-glucose transporter 2 inhibitor, and metformin, pioglitazone, glimepiride or sitagliptin in healthy subjects. Diabetes Obes. Metab.13(1), 47–54 (2011).
   PubMed Web of Science ®Google Scholar
• List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in Type 2 diabetes. Diabetes Care32(4), 650–657 (2009).
   PubMed Web of Science ®Google Scholar
• Wilding JP, Norwood P, T’Joen C, Bastien A, List JF, Fiedorek FT. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care32(9), 1656–1662 (2009).
   PubMed Web of Science ®Google Scholar
• Zhang L, Feng Y, List J, Kasichayanula S, Pfister M. Dapagliflozin treatment in patients with different stages of Type 2 diabetes mellitus: effects on glycaemic control and body weight. Diabetes Obes. Metab.12(6), 510–516 (2010).
   PubMed Web of Science ®Google Scholar
• Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in Type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, Phase 3 trial. Diabetes Care33(10), 2217–2224 (2010).
   PubMed Web of Science ®Google Scholar
• Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with Type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet375(9733), 2223–2233 (2010).
   PubMed Web of Science ®Google Scholar
• Strojek K, Yoon K, Hruba V, Elze M, Langkilde A, Parikh S. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomised, 24-week, double-blind, placebo-controlled trial. Diabetes Obes. Metab.13(10), 928–938 (2011).
   PubMed Web of Science ®Google Scholar
• Wilding JPH, Woo V, Pahor A, Sugg J, Langkilde A, Parikh S. Effect of dapagliflozin, a novel insulin-independent treatment, over 48 weeks in patients with type 2 diabetes poorly controlled with insulin. Diabetologia53(Suppl. 1), (2010) (Abstract s348).
   Google Scholar
• 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 Care34(9), 2015–2022 (2011).
   PubMed Web of Science ®Google Scholar
• Hinnen D, Parikh S, Ying L, Sugg J, List J. Dapagliflozin as monotherapy or as add-on therapy improves glycemic control in patients with Type 2 diabetes. Presented at: American Academy of Nurse Practitioners 26th National Conference. Las Vegas, NV, USA, 22–26 June 2011.
   Google Scholar
• Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care26(2), 510–513 (2003).
   PubMed Web of Science ®Google Scholar
• Muller LM, Gorter KJ, Hak E et al. Increased risk of common infections in patients with Type 1 and Type 2 diabetes mellitus. Clin. Infect. Dis.41(3), 281–288 (2005).
   PubMed Web of Science ®Google Scholar
• Hoepelman AIM, Meiland R, Geerlings SE. Pathogenesis and management of bacterial urinary tract infections in adult patients with diabetes mellitus. Int. J. Antimicrob. Agents22, s35–s43 (2003).
   PubMed Web of Science ®Google Scholar
• Boyko EJ, Lipsky BA. Infection and diabetes. In: Infection and diabetes (2nd Edition). Harris MI, Cowie CC, Stern MP, Boyko EJ, Reiber GE, Bennet PH (Eds). National Institutes of Health, Bethesda, MD, USA, 485–499 (1995).
   Google Scholar
• List J, Ley S, Ptaszynska A et al. Characterization of genital infections in the setting of pharmacologically induced glucosuria. Presented at: American Diabetes Association 71st Scientific Sessions. San Diego, CA, USA, 24–28 June 2011.
   Google Scholar
• Pfister M, Whaley JM, Zhang L, List JF. Inhibition of SGLT2: a novel strategy for treatment of Type 2 diabetes mellitus. Clin. Pharmacol. Ther.89(4), 621–625 (2011).
   PubMed Web of Science ®Google Scholar
• Bailey CJ, Gross JL, Yadav M, Iqbal N, Mansfield TA, List JF. Long-term efficacy of dapagliflozin as add-on to metformin (MET) in T2DM inadequately controlled with MET alone. Presented at: American Diabetes Association 71st Scientific Sessions. San Diego, CA, USA, 24–28 June 2011.
   Google Scholar
• Nauck M, Del Prato S, Rohwedder K, Theuerkauf A, Langkilde AM, Parikh SJ. Long-term efficacy and safety of add-on dapagliflozin vs add-on glipizide in patients with T2DM inadequately controlled with metformin: 2-year results. Presented at: American Diabetes Association 71st Scientific Sessions. San Diego, CA, USA, 24–28 June 2011.
   Google Scholar
• Parikh S, Johnsson KM, Ptaszynska A, Schmitz B, Sugg JE, List JF. Characterization of urinary tract infections in the setting of pharmacologically induced glucosuria. Presented at: American Diabetes Association 71st Scientific Sessions. San Diego, CA, USA, 24–28 June 2011.
   Google Scholar
• Chen J, Williams S, Ho S et al. Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members. Diabetes Therapy1(2), 57–92 (2010).
   PubMedGoogle Scholar
• 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), 1004–1012 (2010).
   PubMed Web of Science ®Google Scholar
• Rosenstock J, Polodori D, Zhao Y et al. Canagliflozin, an inhibitor of sodium glucose co-transporter 2, improves glycaemic control, lowers body weight, and improves β cell function in subjects with Type 2 diabetes on background metformin. Diabetologia53(Suppl. 1), (2010) (Abstract S351).
   Google Scholar
• Salsali A, Bastien A, Mansfield T, Ying L, Ravichandran S, List J. Dapagliflozin improves hyperglycemia and β-cell function without increasing hypoglycemic episodes in patients with Type 2 diabetes mellitus. Presented at: American Association of Clinical Endocrinologists, 20th Annual Meeting and Clinical Congress. San Diego, CA, USA, 13–17 April 2011.
   Google Scholar
• Rossing P, de Zeeuw D. Need for better diabetes treatment for improved renal outcome. Kidney Int.79(Suppl. 120), S28–S32 (2011).
   Web of Science ®Google Scholar
• Ferrannini E, Seman LJ, Seewaldt-Becker E, Hantel S, Pinnetti S, Woerle HJ. The potent and highly selective sodium-glucose co-transporter (SGLT-2) inhibitor BI10773 is safe and efficacious as monotherapy in patients with Type 2 diabetes mellitus. Diabetologia53(Suppl. 1), (2010) (Abstract S351).
   Google Scholar
• Kashiwaga A, Utsuno A, Kazuta K, Yoshida S, Kageyama S. ASP1941, selective SGLT2 inhibitor, was effective and safe in Japanese healthy volunteers and patients with type 2 diabetes [abstract]. Diabetes59(Suppl. 1), 75-OR (2010).
   Google Scholar
• Schwartz S, Morrow L, Hompesch M et al. Canagliflozin improves glycemic control in subjects with Type 2 diabetes (T2D) not optimally controlled on stable doses of insulin. Diabetes59(Suppl. 1), (2010) (Abstract 564-P).
   Google Scholar
• Sha S, Devineni D, Ghosh A et al. Canagliflozin, a novel inhibitor of sodium glucose co-transporter-2, improves glucose control in subjects with type 2 diabetes and was well tolerated. Diabetes59(Suppl. 1), (2010) (Abstract 568-P).
   Google Scholar
• Schwartz S, Klasen S, Kowalski D, Akinlade B. ASP1941, a novel and selective inhibitor of sodium-glucose co-transporter 2 (SGLT2), reduces fasting plasma glucose in Type 2 diabetes mellitus patients over 28 days. Diabetes59(Suppl. 1), (2010) (Abstract 566P).
   Google Scholar
• Wilding JPH, Woo V, Soler NG, Pahor A, Sugg J, Parikh S. Dapagliflozin in patients with Type 2 diabetes poorly controlled on insulin therapy—efficacy of a novel insulin-independent treatment. Diabetes59(Suppl. 1), (2010) (Abstract 78-OR).
   Google Scholar