Empagliflozin Does Not Increase Fracture Risk in Type 2 Diabetes
More women than men experienced bone fractures with empagliflozin 10 mg or placebo but not with empagliflozin 25 mg.
For patients with type 2 diabetes, empagliflozin does not increase the risk for bone fracture compared with placebo or glimepiride, according to results published in Diabetes Care.
The study included pooled data from participants who were randomly assigned 1:1:1 to empagliflozin 10 mg, empagliflozin 25 mg, or placebo in phase 1 to 3 clinical trials. It also included data from the EMPA-REG H2H-SU trial where participants received empagliflozin 25 mg or glimepiride as an add on to metformin for 104 weeks with a 104-week extension. The researchers used a search of investigator-reported events to evaluate bone fracture adverse events (AEs).
Bone fracture AEs were reported in 2.8% of participants in the empagliflozin 10 mg group (119 of 4221; 1.55/100 patient-years), 2.5% of participants in the empagliflozin 25 mg group (105 of 4196; 1.36/100 patient-years), and 2.9% of participants in the placebo group (123 of 4203; 1.69/100 patient-years).
In the EMPA-REG H2H-SU trial, bone fracture AEs were reported in 4.1% of participants in the empagliflozin group (31 of 765; 1.28/100 patient-years) compared with 4.2% of participants in the glimepiride group (33 of 780; 1.40/100 patient-years).
“It has been suggested that [sodium glucose-linked transporter]2 inhibitors may be associated with an increased risk for bone fractures due to the modulation of renal calcium and phosphate reabsorption as a result of changes in renal sodium and glucose reabsorption,” the researchers wrote. “There were no changes in calcium or phosphate levels with empagliflozin, placebo, or glimepiride in our analyses, and no notable differences in changes in other bone markers with empagliflozin treatment compared with placebo or glimepiride treatment.”
The studies that provided data for these analyses were funded by the Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Tove Anderson and Elizabeth Ng of FleishmanHillard Fishburn, London, UK, during the preparation of this manuscript.
Kohler S, Kaspers S, Salsali A, Zeller C, Woerle HJ. 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 [published online June 15, 2018]. Diabetes Care. doi:10.2337/dc17-1525