A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes

Diabetes Obes Metab. 2013 Aug;15(8):721-8. doi: 10.1111/dom.12081. Epub 2013 Mar 4.

Abstract

Aim: This Phase IIb, randomized, double-blind, placebo-controlled trial evaluated the efficacy, safety, tolerability and pharmacokinetics of empagliflozin in patients with type 2 diabetes.

Methods: Four hundred and eight patients (treatment-naïve or after a 4-week wash-out period) were randomized to receive empagliflozin 5, 10 or 25 mg once daily, placebo or open-label metformin for 12 weeks. The primary endpoint was change in haemoglobin A1c (HbA1c) after 12 weeks.

Results: After 12 weeks' treatment, empagliflozin showed dose-dependent reductions in HbA1c from baseline [5 mg: -0.4%, 10 mg: -0.5%, 25 mg: -0.6%; all doses p < 0.0001 vs. placebo (+0.09%)]. Fasting plasma glucose (FPG) decreased with empagliflozin [5 mg: -1.29 mmol/l, 10 mg: -1.61 mmol/l, 25 mg: -1.72 mmol/l; all doses p < 0.0001 vs. placebo (+0.04 mmol/l)]. Body weight decreased in all empagliflozin groups (all doses p < 0.001 vs. placebo). The incidence of adverse events (AEs) was similar in the placebo (32.9%) and empagliflozin (29.1%) groups. The most frequently reported AEs on empagliflozin were pollakiuria (3.3% vs. 0% for placebo), thirst (3.3% vs. 0% for placebo) and nasopharyngitis (2.0% vs. 1.2% for placebo). AEs consistent with urinary tract infections (UTIs) were reported in four (1.6%) patients on empagliflozin vs. one (1.2%) on placebo. Genital infections were reported in five (2%) patients on empagliflozin vs. 0% on placebo. No UTIs or genital infections led to premature discontinuation.

Conclusions: In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG, and reductions in body weight compared with placebo. Empagliflozin was well-tolerated with a favourable safety profile.

Keywords: BI 10773; FPG; HbA1c; SGLT2 inhibitor; body weight; empagliflozin; tolerability.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Argentina / epidemiology
  • Benzhydryl Compounds / administration & dosage*
  • Benzhydryl Compounds / adverse effects
  • Blood Glucose
  • Body Weight
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Europe / epidemiology
  • Female
  • Glucosides / administration & dosage*
  • Glucosides / adverse effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Nasopharyngitis / chemically induced*
  • Nasopharyngitis / epidemiology
  • Republic of Korea / epidemiology
  • Russia / epidemiology
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Taiwan / epidemiology
  • Thirst
  • Treatment Outcome
  • Ukraine / epidemiology
  • Urination Disorders / chemically induced*
  • Urination Disorders / epidemiology
  • Weight Loss

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • hemoglobin A1c protein, human
  • Metformin
  • empagliflozin