Biotransformation and mass balance of the SGLT2 inhibitor empagliflozin in healthy volunteers

References

• Barnett AH, Mithal A, Manassie J, et al. (2014). Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2:369–84
   PubMed Web of Science ®Google Scholar
• Bristol-Myers Squibb/AstraZeneca. Forxiga (dapagliflozin) summary of product characteristics. (2014). Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002322/human_med_001546.jsp&mid=WC0b01ac058001d124 [last accessed 15 Sept 2014]
   Google Scholar
• DeFronzo RA. (2009). Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58:773–95
   PubMed Web of Science ®Google Scholar
• DeFronzo RA, Davidson JA, del Prato S. (2012). The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab 14:5–14
   PubMed Web of Science ®Google Scholar
• Esposito K, Chiodini P, Bellastella G, et al. (2012). Proportion of patients at HbA1c target <7% with eight classes of antidiabetic drugs in type 2 diabetes: systematic review of 218 randomized controlled trials with 78945 patients. Diabetes Obes Metab 14:228–33
   PubMed Web of Science ®Google Scholar
• Gerich JE. (2010). Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med 27:136–42
   PubMed Web of Science ®Google Scholar
• Grempler R, Thomas L, Eckhardt M, et al. (2012). Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab 14:83–90
   PubMed Web of Science ®Google Scholar
• Haering HU, Merker L, Seewaldt-Becker E, et al. (2013). Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 36:3396–404
   PubMed Web of Science ®Google Scholar
• Haering HU, Merker L, Seewaldt-Becker E, et al. (2014). Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 37:1650–9
   PubMed Web of Science ®Google Scholar
• Heise T, Seewaldt-Becker E, Macha S, et al. (2013a). Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks' treatment with empagliflozin once daily in patients with type 2 diabetes. Diabetes Obes Metab 15:613–21
   PubMed Web of Science ®Google Scholar
• Heise T, Seman L, Macha S, et al. (2013b). Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising doses of empagliflozin in patients with type 2 diabetes mellitus. Diabetes Ther 4:331–45
   PubMed Web of Science ®Google Scholar
• International Diabetes Federation. (2013). IDF diabetes atlas. Executive Summary. Available from: http://www.idf.org/sites/default/files/EN_6E_Atlas_Exec_Sum_1.pdf [last accessed 15 Sept 2014]
   Google Scholar
• Inzucchi SE, Bergenstal RM, Buse JB, et al. (2012). Management of hyperglycemia 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). Diabetes Care 35:1364–79
   PubMed Web of Science ®Google Scholar
• Kovacs CS, Seshiah V, Swallow R, et al. (2014). 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 16:147–58
   PubMed Web of Science ®Google Scholar
• Macha S, Mattheus M, Halabi A, et al. (2014a). Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. Diabetes Obes Metab 16:215–22
   PubMed Web of Science ®Google Scholar
• Macha S, Rose P, Mattheus M, et al. (2014b). Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with hepatic impairment. Diabetes Obes Metab 16:118–23
   PubMed Web of Science ®Google Scholar
• Mamidi RN, Cuyckens F, Chen J, et al. (2014). Metabolism and excretion of canagliflozin in mice, rats, dogs, and humans. Drug Metab Dispos 42:903–16
   PubMed Web of Science ®Google Scholar
• Obermeier M, Yao M, Khanna A, et al. (2010). In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans. Drug Metab Dispos 38:405–14
   PubMed Web of Science ®Google Scholar
• Roden M, Weng J, Eilbracht J, et al. (2013). Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol 1:208–19
   PubMed Web of Science ®Google Scholar
• Seman L, Macha S, Nehmiz G, et al. (2013). Empagliflozin (BI 10773), a potent and selective SGLT-2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clinical Pharm in Drug Dev 2:152–61
   PubMed Web of Science ®Google Scholar
• U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Food and Drug Administration. (2008). Guidance for Industry: Safety Testing of Drug Metabolites. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm079266.pdf [last accessed 15 Sep 2014]
   Google Scholar