Format

Send to

Choose Destination
Ann Intern Med. 2019 Jan 1. doi: 10.7326/M18-0567. [Epub ahead of print]

Fracture Risk After Initiation of Use of Canagliflozin: A Cohort Study.

Author information

1
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and Clinician Scientist Training Program, Department of Medicine, University of Toronto, Toronto, Ontario, Canada (M.F.).
2
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (S.C.K., S.S., D.K., E.P.).
3
Sunnybrook Hospital and University of Toronto, Toronto, Ontario, Canada (D.A.R.).

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.

PMID:
30597484
DOI:
10.7326/M18-0567

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center