Ontology highlight
ABSTRACT: Background
Sodium-glucose cotransporter-2 inhibitors promote glycosuria, resulting in possible effects on calcium, phosphate, and vitamin D homeostasis. Canagliflozin is associated with decreased bone mineral density and a potential increased risk for fracture.Objective
To estimate risk for nonvertebral fracture among new users of canagliflozin compared with a glucagon-like peptide-1 (GLP-1) agonist.Design
Population-based new-user cohort study.Setting
Two U.S. commercial health care databases providing data on more than 70 million patients from March 2013 to October 2015.Patients
Persons with type 2 diabetes who initiated use of canagliflozin were propensity score-matched in a 1:1 ratio to those initiating use of a GLP-1 agonist.Measurements
The primary outcome was a composite end point of humerus, forearm, pelvis, or hip fracture requiring intervention. Secondary outcomes included fractures at other sites. A fixed-effects meta-analysis that pooled results from the 2 databases provided an overall hazard ratio (HR).Results
79 964 patients initiating use of canagliflozin were identified and matched to 79 964 patients initiating use of a GLP-1 agonist. Mean age was 55 years, 48% were female, average baseline hemoglobin A1c level was 8.7%, and 27% were prescribed insulin. The rate of the primary outcome was similar for canagliflozin (2.2 events per 1000 person-years) and GLP-1 agonists (2.3 events per 1000 person-years), with an overall HR of 0.98 (95% CI, 0.75 to 1.26). Risk for pelvic, hip, humerus, radius, ulna, carpal, metacarpal, metatarsal, or ankle fracture was also similar for canagliflozin (14.5 events per 1000 person-years) and GLP-1 agonists (16.1 events per 1000 person-years) (overall HR, 0.92 [CI, 0.83 to 1.02]).Limitation
Unmeasured confounding, measurement error, and low fracture rate.Conclusion
In this study of middle-aged patients with type 2 diabetes and relatively low fracture risk, canagliflozin was not associated with increased risk for fracture compared with GLP-1 agonists.Primary funding source
Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics.
SUBMITTER: Fralick M
PROVIDER: S-EPMC6602870 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
Fralick Michael M Kim Seoyoung C SC Schneeweiss Sebastian S Kim Dae D Redelmeier Donald A DA Patorno Elisabetta E
Annals of internal medicine 20190101 3
<h4>Background</h4>Sodium-glucose cotransporter-2 inhibitors promote glycosuria, resulting in possible effects on calcium, phosphate, and vitamin D homeostasis. Canagliflozin is associated with decreased bone mineral density and a potential increased risk for fracture.<h4>Objective</h4>To estimate risk for nonvertebral fracture among new users of canagliflozin compared with a glucagon-like peptide-1 (GLP-1) agonist.<h4>Design</h4>Population-based new-user cohort study.<h4>Setting</h4>Two U.S. co ...[more]