Effect of SGLT2 inhibitors on fractures, BMD, and bone metabolism markers in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

This meta-analysis aims to evaluate the impact of Sodium Glucose Transporter 2 (SGLT2) inhibitors on fractures, bone mineral density (BMD), and bone metabolism markers in type 2 diabetes mellitus (T2DM) patients. Pooled relative risk (RR) with 95% confidence interval (CI) assessed the relationship between SGLT2 inhibitors and fracture risk. Weighted mean difference (WMD) with 95% CI explored the correlation between SGLT2 inhibitors and BMD, as well as bone metabolism markers. A total of 20 randomised controlled trials (RCTs) involving 12,764 patients were analysed. No significant association emerged between SGLT2 inhibitor use and elevated fracture risk (pooled RR = 1.21, 95% CI [0.95, 1.54], I2 = 22%). Furthermore, SGLT2 inhibitors exhibited no substantial effects on BMD changes at the lumbar spine (WMD = -0.02, 95% CI [-0.38, 0.34]), femoral neck (WMD = 0.11, 95% CI [-0.28, 0.50]), total hip (WMD = -0.20, 95% CI [-0.41, 0.01]), and distal forearm (WMD = -0.20, 95% CI [-0.62, 0.22]). Similarly, no notable impact of SGLT2 inhibitors on bone metabolism markers, including CTX (WMD = 0.04, 95% CI [-0.02, 0.09]), P1NP (WMD = 1.06, 95% CI [-0.44, 2.57]), PTH (WMD = 0.34, 95% CI [-0.07, 0.75]), calcium (WMD = 0.01, 95% CI [-0.02, 0.04]), and phosphate (WMD = 2.37, 95% CI [-0.76, 5.49]). The findings suggest that the utilization of SGLT2 inhibitors is not significantly linked to an elevated risk of fractures in individuals with T2DM. However, further clinical investigations and extended follow-up periods are warranted to establish more conclusive determinations.