Compared with glucagon-like peptide 1 (GLP-1) receptor agonists, initiation of canagliflozin use for the treatment of type 2 diabetes (T2D) was not associated with increased risk for fracture, according to study results published in Annals of Internal Medicine.

The investigators of this population-based, new-user cohort study sought to estimate the risk for nonvertebral, low-impact fracture among individuals with T2D initiating treatment with canagliflozin compared with GLP-1 receptor agonists.

The study sample was drawn from 2 United States commercial insurance claims databases and included 79,964 adults with T2D who had been newly prescribed canagliflozin matched to 79,964 adults who were newly prescribed GLP-1 agonists using propensity scoring. 

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A composite end point of humerus, forearm, pelvis, or hip fracture requiring intervention (surgery, casting, or splinting) was the primary outcome of interest; fractures without intervention and fractures at other sites were included as secondary outcomes. The study investigators performed a fixed-effects meta-analysis to provide an overall hazard ratio (HR) by pooling results from the 2 databases.

In the matched cohort, the mean participant age was approximately 55 years and the average baseline glycemic level was 8.7%; 27% of the total cohort was prescribed insulin, while 57% was prescribed metformin. The rate of composite pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention was similar among canagliflozin users (2.3 events/1000 person-years) and GLP-1 receptor agonist users (2.2 events/1000 person-years), with an overall HR of 0.98 (95% CI, 0.75-1.26). Risk for incident pelvic, hip, humerus, radius, ulna, carpal, metacarpal, metatarsal, or ankle fracture was also similar between users of canagliflozin (14.5 events/1000 person-years) and GLP-1 receptor agonists (16.1 events/1000 person-years), with an overall HR of 0.92 (95% CI, 0.83-1.02). These results remained robust across different sensitivity and subgroup analyses.

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Limitations to the study included a relatively young cohort with low fracture rates, which may make findings less applicable to older patients with higher baseline risk.

The overall rate of fracture in adults with T2D was comparably low in patients newly treated with canagliflozin or GLP-1 agonists. The study investigators suggested that canagliflozin is safe to treat patients with diabetes without other risk factors for fracture.

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Fralick M, Kim SC, Schneeweiss S, Kim D, Redelmeier DA, Patorno E. Fracture risk after initiation of use of canagliflozin: a cohort study [published online January 1, 2019]. Ann Intern Med. doi:10.7326/M18-0567