Boston—Sodium-glucose cotransporter-2 (SGLT2) inhibitors appear to reduce major adverse cardiovascular events and reduce the risk of heart failure in type 2 diabetes (T2D) patients. As a result, increasing clinical guidelines recommend the class as a second-line therapy when metformin doesn’t resolve hyperglycemia.

But some research has cautioned about side effects, including effect on bone density. In light of that, a new study looked at the risk for nonvertebral fracture among new users of one SGLT2 inhibitor, canagliflozin, compared with a glucagon-like peptide-1 (GLP-1) agonist.

The population-based, new-user cohort study, led by researchers from Brigham and Women’s Hospital and Harvard Medical School, took into account that SGLT2 inhibitors can promote glycosuria, resulting in possible effects on calcium, phosphate, and vitamin D homeostasis. The Annals of Internal Medicine report notes that canagliflozin is associated with decreased bone mineral density and a theoretical increased risk for fracture.

The study used two U.S. commercial healthcare databases providing data on more than 70 million patients from March 2013 to October 2015. Included were 79,964 patients with T2D who initiated use of canagliflozin; they were propensity score–matched in a 1:1 ratio to those initiating use of a GLP-1 agonist. The mean age of participants was 55 years, and 48% were female. Average baseline hemoglobin A1c level was 8.7%, and 27% were prescribed insulin.

Defined as the primary outcome was a composite end point of humerus, forearm, pelvis, or hip fracture requiring intervention, while secondary outcomes included fractures at other sites. A fixed-effects meta-analysis that pooled results from the two databases provided an overall hazard ratio.

Results indicate that the rate of the primary outcome was similar for canagliflozin (2.2 events per 1,000 person-years) and GLP-1 agonists (2.3 events per 1,000 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 1,000 person-years) and GLP-1 agonists (16.1 events per 1,000 person-years) (overall HR, 0.92 [CI, 0.83 to 1.02]).

“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,” study authors conclude.

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