Safety and tolerability of empagliflozin in East Asian patients with type 2 diabetes: Pooled analysis of phase I-III clinical trials

J Diabetes Investig. 2019 Mar;10(2):418-428. doi: 10.1111/jdi.12910. Epub 2018 Sep 20.

Abstract

Aims/introduction: We investigated the safety and tolerability of empagliflozin (EMPA) in East Asian patients with type 2 diabetes.

Materials and methods: Data were pooled from participants with type 2 diabetes evenly randomized to a placebo, EMPA 10 mg or EMPA 25 mg in 15 phase I-III trials. Adverse events (AEs) were analyzed in the subgroup of trial participants from East Asian countries/regions.

Results: In total, 709, 724 and 708 East Asian trial participants with type 2 diabetes received a placebo, EMPA 10 mg and EMPA 25 mg, respectively; total exposure was 953, 1,072, and 1,033 patient-years in these groups, respectively. The EMPA and placebo groups had similar incidences of severe AEs, serious AEs and AEs leading to discontinuation. Incidences of hypoglycemia differed according to anti-diabetes medication used at baseline. Higher rates of events consistent with genital infection were observed with EMPA (EMPA 1.5-1.7/100, placebo 0.2/100 patient-years). Rates of AEs consistent with volume depletion were comparable among treatment groups (0.8-1.4/100 patient-years), but in trial participants aged ≥65 years, the rate was greater with EMPA 25 mg (EMPA 25 mg 3.5/100, placebo 2.0/100 patient-years). Incidences of events consistent with urinary tract infection, thromboembolic events, renal events, hepatic AEs, diabetic ketoacidosis, fractures and lower limb amputation were similar between EMPA and the placebo.

Conclusions: In the present pooled analysis, EMPA was well tolerated in East Asian type 2 diabetes patients based on >2,100 patient-years' exposure, consistent with results from the overall analysis population.

Keywords: Adverse drug event; Genital infection; Sodium-glucose cotransporter 2 inhibitor.

MeSH terms

  • Aged
  • Benzhydryl Compounds / therapeutic use*
  • Biomarkers / analysis*
  • Blood Glucose / analysis
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Female
  • Follow-Up Studies
  • Glucosides / therapeutic use*
  • Glycated Hemoglobin / analysis
  • Humans
  • Incidence
  • Japan / epidemiology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Safety
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*

Substances

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