South Korea: A claims-based study involving two independent Korean cohorts revealed that SGLT2 inhibitors are associated with a lower or similar risk of fracture versus incretin-based antidiabetic agents in postmenopausal women with type 2 diabetes (T2D). The study findings were published in JAMA Network Open on September 26, 2023.
The researchers showed that new users of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) had a lower risk for incident fractures versus those started on a DPP-4 inhibitor (weighted HR 0.78). In the second cohort, the fracture risk with SGLT2 inhibitors versus GLP-1 receptor agonists was no different (weighted HR 0.92).

Postmenopausal women with T2D are known to be susceptible to fractures due to the interaction of increased blood glucose levels and estrogen deficiency. There is a lack of existing evidence in this high-risk population despite continued concerns of fractured risks tied to SGLT2 inhibitors. To fill this knowledge gap, Hwa Yeon Ko, Sungkyunkwan University, Suwon, South Korea, and colleagues aimed to assess fracture risk associated with SGLT2 inhibitors versus incretin-based drugs of GLP1RA (glucagon-like peptide 1 receptor agonists) and DPP4i (dipeptidyl-peptidase 4 inhibitors), separately in postmenopausal women with type 2 diabetes.
For this purpose, the researchers conducted an active-comparator, new-user cohort study using nationwide claims data from Korea from 2013 to 2020. It included postmenopausal individuals (aged ≥45 years) with type 2 diabetes.
The primary outcome of the study was calculated as overall fractures comprising humerus, hip, vertebral, and distal radius fractures. Follow-up of the patients was done from the day after drug initiation until drug discontinuation (90-day grace period), earliest of outcome occurrence, or switch, death, or end of the study period. Hazard ratios (HRs) were estimated using weighted Cox models after propensity score fine stratification.
The study led to the following findings:
Among 37 530 (mean age, 60.6 years) and 332 004 (mean age, 60.6 years) new users of SGLT2i and DPP4i, respectively, a lower rate of incident overall fractures was presented with SGLT2i versus DPP4i (weighted HR, 0.78).
Among 111 835 (mean age, 61.4 years) and 8177 (mean age, 61.1 years) new users of SGLT2i and GLP1RA, respectively, no association with an increased risk of overall fractures was presented with SGLT2i versus GLP1RA (weighted HR, 0.92).
Results from several subgroup and sensitivity analyses presented consistent results from the main analysis.
"The findings suggest that the use of SGLT2 inhibitors was not tied to an increased risk of overall fractures among postmenopausal patients with T2D," the researchers wrote. "The result remained consistent regardless of the particular incretin-based drug as an active comparator."
"These findings indicate that SGLT2 inhibitor has either similar or lower fracture risks 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," they concluded.
Reference:
Ko HY, Bea S, Jeong HE, et al. Sodium-Glucose Cotransporter 2 Inhibitors vs Incretin-Based Drugs and Risk of Fractures for Type 2 Diabetes. JAMA Netw Open. 2023;6(9):e2335797. doi:10.1001/jamanetworkopen.2023.35797