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SGLT2 Inhibitors Not Linked with Increased Fracture Risk Among Postmenopausal Type 2 Diabetes Patients

Treatment with SGLT2 inhibitors did not appear to be linked with an increased risk for fractures compared with DPP-4 inhibitors and GLP-1 receptor agonists among Korean postmenopausal patients with type 2 diabetes, according to findings in JAMA Network Open.

“SGLT2 inhibitors have demonstrated substantial cardio-kidney benefits across several pivotal randomized clinical trials. However, because of its unique glucose-controlling mechanism through kidney proximal tubules, SGLT2 inhibitors may also affect calcium and phosphate homeostasis. This may compromise bone mineral density.

- Hwa Yeon Ko, PharmD, school of pharmacy at Sungkyunkwan University, South Korea. 

The researchers performed a nationwide observational study of postmenopausal patients in Korea who were part of the country’s national health insurance database and who all had type 2 diabetes. The study ran from 2013 to 2020. In this active-comparator, new-user cohort study, researchers reviewed data from claims in the national database to evaluate the risk of fracture associated with SGLT2 inhibitors and GLP-1 agonists, respectively. The main outcome was overall fractures in this population. 

The study authors followed patients from the day after they started medication until the first occurrence of fracture, death, drug discontinuation or switching to another drug, or the end of the study period. The researchers used weighted Cox models to estimate the hazard ratios for fracture associated with the study drugs. 

A total of 37,530 patients were considered new users of SGLT2 inhibitors, and 332,004 were new users of DPP-4 inhibitors during the study period. The patients in both populations were a mean of 60.6 years old, and all were a minimum of 45 years of age. 

The weighted incidence of overall fractures during a mean of 1.45 years of follow-up was 1.41 events per person-years for those taking SGLT2 inhibitors, whereas the incidence was 1.81 events per 100 person-years for those taking DPP-4 inhibitors. Compared with DPP-4 inhibitors, the overall rate of incident fractures was lower among patients who took SGLT2 inhibitors, the researchers reported (weighted hazard ratio [HR] = 0.78; 95% CI, 0.72-0.84). 

When the researchers compared new users of SGLT2 inhibitors and new users of GLP-1 agonists, SGLT2 inhibitors were not associated with an increased risk of overall fractures (weighted HR = 0.92; 95% CI, 0.68-1.24). 

The researchers acknowledged that the study was susceptible to some limitations, including residual confounding from unmeasured covariates, the small portion of patients taking GLP-1 agonists, the fact that the population was entirely Korean and therefore not generalizable to the real-world population, and the lack of a standardized definition of “postmenopausal.” 

“The use of SGLT2 inhibitors was not associated with an increased risk of overall fractures among postmenopausal patients with type 2 diabetes. This result remained consistent irrespective of the particular incretin-based drug as an active comparator. These findings indicate that SGLT2 inhibition has either similar or lower risks of fractures than incretin-based drugs even in a population at higher risk for fractures, providing reassurance to and helping health care professionals with their clinical decision-making.”

- Hwa Yeon Ko, PharmD, school of pharmacy at Sungkyunkwan University, South Korea.




Disclosures: Ko declared no financial ties to drug makers. Some authors declared financial ties to drug makers. See full study for details. The study was funded by the Ministry of Food and Drug Safety.

Photo Credit: Getty Images.

By Andrew John, MD /alert Contributor

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