Analysis of Fractures in Patients With Type 2 Diabetes Treated With Empagliflozin in Pooled Data From Placebo-Controlled Trials and a Head-to-Head Study Versus Glimepiride

Diabetes Care. 2018 Aug;41(8):1809-1816. doi: 10.2337/dc17-1525. Epub 2018 Jun 15.

Abstract

Objective: To assess the effect of empagliflozin on bone fractures and bone mineral density in patients with type 2 diabetes in pooled placebo-controlled trial data and a head-to-head study versus glimepiride.

Research design and methods: Pooled data were analyzed from patients who were randomized 1:1:1 to empagliflozin 10 mg, empagliflozin 25 mg, or placebo in phase I-III clinical trials. Data were also analyzed from the EMPA-REG H2H-SU trial in which patients received empagliflozin 25 mg or glimepiride as an add-on to metformin for 104 weeks with a 104-week extension. Bone fracture adverse events (AEs) were evaluated through a search of investigator-reported (nonadjudicated) events.

Results: In the pooled analysis, bone fracture AEs were reported in 119 of 4,221 (2.8%), 105 of 4,196 (2.5%), and 123 of 4,203 (2.9%) patients in the empagliflozin 10 mg, empagliflozin 25 mg, and placebo groups, respectively (rates of 1.55, 1.36, and 1.69/100 patient-years, respectively). In the EMPA-REG H2H-SU trial, bone fracture AEs were reported in 31 of 765 (4.1%) patients receiving empagliflozin 25 mg and in 33 of 780 (4.2%) patients receiving glimepiride (rates of 1.28 and 1.40/100 patient-years, respectively).

Conclusions: Empagliflozin did not increase the risk of bone fracture compared with placebo in a pooled analysis of >12,000 patients or compared with glimepiride in a 4-year head-to-head study.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use*
  • Bone Density / drug effects
  • Clinical Trials, Phase I as Topic / statistics & numerical data
  • Clinical Trials, Phase II as Topic / statistics & numerical data
  • Clinical Trials, Phase III as Topic / statistics & numerical data
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Female
  • Fractures, Bone / chemically induced
  • Fractures, Bone / epidemiology*
  • Glucosides / adverse effects
  • Glucosides / therapeutic use*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Placebos
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Sulfonylurea Compounds / adverse effects
  • Sulfonylurea Compounds / therapeutic use*

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Placebos
  • Sulfonylurea Compounds
  • glimepiride
  • Metformin
  • empagliflozin