medwireNews: Research based on insurance claims data indicates that new users of the sodium-glucose cotransporter-2 inhibitor canagliflozin are no more likely to experience a fracture than new users of glucagon-like peptide (GLP)-1 receptor agonists.
However, the authors of an editorial on the study, which is published in the Annals of Internal Medicine, note that although the results “may reassure health care providers,” they may not be completely conclusive.
William Leslie (University of Manitoba, Winnipeg, Canada) and John Schousboe (University of Minnesota, Minneapolis, USA) point out the duration of exposure to canagliflozin was “usually brief” and that the study population was younger (average age approximately 55 years) than those commonly recruited to randomized trials, and included a higher proportion of men (52%), equating to a relatively low fracture risk.
Indeed, there were just 118 fractures (of the humerus, forearm, pelvis, or hip) that required intervention among 79,964 new users of canagliflozin and 112 among an equal number of propensity-matched new users of GLP-1 receptor agonists, equating to rates of 2.2 and 2.3 per 1000 person–years, respectively.
Average medication exposure was around 35 weeks for canagliflozin users and 32 weeks for GLP-1 receptor agonist users. However, Michael Fralick (Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA) and co-researchers found association between canagliflozin and fracture risk when they restricted the analysis to patients with at least 6 months of follow-up.
And they note that in the CANVAS trial an increased risk for fracture emerged within 12 weeks of patients starting on canagliflozin versus placebo. There was no such effect in the CANVAS-R trial, however.
In the current analysis, there was also no sign of an increased fracture risk with canagliflozin in patients older than 60 years of age or when the analysis was expanded to include fractures that did not require intervention and fractures at other sites (carpal, metacarpal, metatarsal, and ankle).
In their editorial, Leslie and Schousboe say that more information is needed concerning the effect of canagliflozin on fracture risk in patients with “advanced age, very low bone mineral density, prior fracture, frailty, or a combination of these factors.”
In the meantime, they advise caution when using canagliflozin in such patients, “with particular attention given to hydration status and fall risk.”
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