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Canagliflozin not associated with fracture risk

Research published in Annals of Internal Medicine indicated no increased risk for fracture with the use of canagliflozin among patients with diabetes.

“Sodium–glucose cotransporter-2 (SGLT2) inhibitors promote glycosuria, resulting in possible effects on calcium, phosphate and vitamin D homeostasis,” Michael Fralick, MD, SM, from Brigham and Women's Hospital and Harvard Medical School, and colleagues wrote.

“Canagliflozin, unlike other SGLT2 inhibitors, is associated with decreased bone mineral density,” they added. “Patients with diabetes mellitus are at increased risk for fractures, and canagliflozin may exacerbate this risk.”

Fralick and colleagues reviewed data from two U.S. commercial health care databases to determine the risk for nonvertebral fracture associated with new use of canagliflozin compared with a glucagon-like peptide-1 (GLP-1) agonist. The researchers identified 79,964 patients with type 2 diabetes who initiated use of canagliflozin. These patients were propensity score-matched 1:1 to patients who initiated use of a GLP-1 agonist.

The primary endpoint was a humerus, forearm, pelvis or hip fracture that required intervention.

Participants had a mean age of 55 years and an average baseline HbA1c of 8.7%. Insulin was prescribed to 27% of participants.

The researchers found that participants taking canagliflozin had similar rates of humerus, forearm, pelvis or hip fractures requiring intervention to those taking a GLP-1 agonist (2.2 events vs. 2.3 events per 1,000 person-years; HR = 0.98; 95% CI, 0.75-1.26).

There were also similar risks for pelvic, hip, humerus, radius, ulna, carpal, metacarpal, metatarsal, or ankle fractures among canagliflozin and GLP-1 agonist users (14.5 events vs. 16.1 events per 1,000 person-years; HR = 0.92; 95% CI, 0.83-1.02).

“Our results are most relevant to patients with diabetes who do not have other risk factors for fracture, such as older age or previous fracture,” Fralick and colleagues concluded. “These results should be reassuring to patients and physicians who are considering the potential risks and benefits of canagliflozin. Our findings also raise the question of whether the increase in fracture risk reported in CANVAS is limited to patients with high baseline risk.”

In an accompanying editorial, William D. Leslie, MD, MSc, from the University of Manitoba, Canada, and John T. Schousboe, MD, PhD, from Park Nicollet Clinic and HealthPartners Institute and University of Minnesota, wrote that the study by Fralick and colleagues adds to the growing literature that there is little if any fracture risk with canagliflozin use among patients with diabetes who have a low fracture risk.

However, more research is required to determine if these findings are relevant to patients with diabetes and a high fracture risk, they added.

“Although these data may reassure health care providers that prescribing canagliflozin will not increase fracture risk in their patients with diabetes, caution may still be appropriate when this agent is used in older patients who have high fracture risk, with particular attention given to hydration status and fall risk,” they concluded. – by Alaina Tedesco

Disclosures: Fralick, Leslie and Schousboe report no relevant financial disclosures. Please see study for all other authors’ relevant financial disclosures.