Cohort Study Finds No Increased Fracture Risk with Canagliflozin

Canagliflozin, recently approved for the reduction of heart attack and stroke risk in type 2 diabetics with known cardiovascular disease, was not associated with increased fracture risk, a new study suggests.

Due to the tendency for sodium-glucose cotransporter-2 (SGLT-2) inhibitors to promote glycosuria (which has downstream effects on calcium, phosphate, vitamin D homeostasis), and canagliflozin’s association with decreased bone mineral density, a concern was raised about potential increased risk for fracture in patients taking canagliflozin.

Researchers for the new cohort study published in the Annals of Internal Medicine compared the risk for nonvertebral fracture in users of canagliflozin, an SGLT2 inhibitor, with risk seen with a glucagon-line peptide-1 (GLP-1) agonist. The study cohort was drawn from two commercial databases with over 70 million patients. Subjects taking canagliflozin were matched (1:1) with those taking a GLP-1 agonist (79,964 patients taking canagliflozin and 79,964 taking a GLP-1 agonist). The primary study outcome was a combined endpoint of humerus, forearm, pelvis or hip fracture requiring medical intervention.

Happy to share the first of my PhD thesis papers looking at risk of fracture in ~200,000 patients prescribed canagliflozin vs GLP1. We found no increased rate of fracture with canagliflozin. Most relevant to pts at low baseline risk of fracture. https://t.co/weIRmX0Yu0 pic.twitter.com/zLokcK60o5

— Michael Fralick (@FralickMike) January 1, 2019

According study results, the rate of the primary study outcome was similar in both cohorts, with an overall hazard ratio of 0.98 (95% CI, 0.75 to 1.26). There were 2.2 events per 1,000 person years in the canagliflozin group compared to 2.3 events per 1,000 person years in the GLP-1 group. The results were similar between study groups for humerus, radios, ulna, carpal, metacarpal, metatarsal, or ankle fracture risk as well (canagliflozin, 14.5 events per 1,000 person years vs. 16.1 events per 1,000 person years; HR=0.92).

Another incredible paper by superstar Mike Fralick! Privilege to be on his thesis committee. I am learning more from him than vice versa! https://t.co/MZ1d8POizZ

— Fahad Razak (@DrFahadRazak) January 1, 2019

“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,” the authors wrote in their conclusion.

A big congrats to @FralickMike 😀 https://t.co/VJpAyj0Gtf

— LKS-CHART (@Chart_DataSci) January 2, 2019

In an accompanying editorial, the piece’s authors noted that “[l]arge health care data sets can provide insight into how approved treatments move from research to clinical practice and can provide additional evidence of effectiveness and safety,” and that the present study “is a good example of how observational data can be exploited to good advantage.”

No Signal. Fracture Risk After Initiation of Use of Canagliflozin | Ann Intern Med | ACP | https://t.co/p6OTy5i1g7

— Daniel J Drucker (@DanielJDrucker) January 1, 2019

As previously reported on DocWire News, canagliflozin was approved in October 2018 by the FDA for the reduction of heart attack, stroke, or cardiovascular death in adults with established cardiovascular disease and type 2 diabetes in October 2018.

Source: Annals of Internal Medicine