Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks' treatment with empagliflozin once daily in patients with type 2 diabetes

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2013-07, Vol.15 (7), p.613-621
• Main Authors: Heise, T., Seewaldt-Becker, E., Macha, S., Hantel, S., Pinnetti, S., Seman, L., Woerle, H. J.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Aged; Benzhydryl Compounds - administration & dosage; Benzhydryl Compounds - adverse effects; Benzhydryl Compounds - pharmacology; Benzhydryl Compounds - therapeutic use; BI 10773; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - urine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; empagliflozin; Female; Germany - epidemiology; Glucose; Glucosides - administration & dosage; Glucosides - adverse effects; Glucosides - pharmacology; Glucosides - therapeutic use; Glycosuria - chemically induced; Glycosuria - epidemiology; Glycosuria - physiopathology; Humans; Hyperglycemia - prevention & control; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Incidence; Male; Membrane Transport Modulators - administration & dosage; Membrane Transport Modulators - adverse effects; Membrane Transport Modulators - pharmacology; Membrane Transport Modulators - therapeutic use; Middle Aged; pharmacodynamics; pharmacokinetics; Polyuria - epidemiology; Polyuria - etiology; SGLT2 inhibitor; Sodium-Glucose Transporter 2 - antagonists & inhibitors; urinary glucose excretion
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12073

ABSTRACT Aim To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of empagliflozin in patients with type 2 diabetes following oral administration of 10, 25 or 100 mg doses once daily over 28 days. Methods A total of 78 patients were assigned to empagliflozin 10 mg (n = 16), 25 mg (n = 16) or 100 mg (n = 30) or placebo (n = 16) for 28 days. Assessments included adverse events (AEs) and pharmacokinetic and pharmacodynamic endpoints. Results Empagliflozin exposure increased dose‐proportionally over the dose range 10–100 mg and showed linear pharmacokinetics with respect to time. Urinary glucose excretion (UGE) increased from baseline to day 1 by 74, 90 and 81 g with empagliflozin 10, 25 and 100 mg, respectively. The increases in UGE were maintained over 28 days with multiple dosing. Virtually no change in UGE was observed in the placebo group. Significant reductions from baseline in mean daily plasma glucose and fasting plasma glucose were observed with empagliflozin compared with placebo. The incidence of AEs was similar in the empagliflozin and placebo groups (50.0, 56.3 and 66.7% with empagliflozin rising doses and 62.5% with placebo). The most frequently reported AEs were pollakiuria (10.3%), nasopharyngitis (9.0%), constipation (9.0%) and headache (7.7%). Conclusions Oral administration of empagliflozin at doses of 10, 25 or 100 mg once daily over 28 days resulted in significant increases in UGE and reductions in blood glucose compared with placebo, and were well tolerated in patients with type 2 diabetes.