Na-dependent glucose transporter-2 inhibitors, bone mineral density, and fracture risk in type-2 diabetes mellitus with osteoporosis: A meta-analysis of 2,000 patients.

OBJECTIVE: We evaluated the effects of sodium-dependent glucose transporter 2 inhibitors (SGLT2i) on bone mineral density (BMD) and fracture risk in patients with type 2 diabetes mellitus (T2DM) and osteoporosis. MATERIALS AND METHODS: Randomized controlled trials (RCTs) published before April 2024 were systematically searched in PubMed, MEDLINE, Web of Science, the Cochrane Library, and EMBASE. Quality assessment was performed by Cochrane Risk of Bias 2 tool. RevMan 5.3 software was employed to conduct meta-analysis. The outcome indicators included glycosylated hemoglobin A1c (HbA1c), BMD change, and fracture incidence rate. RESULTS: A total of 8 studies covering 1,998 subjects were included (1,094 in the SGLT2i group and 904 in the control group). Analysis of 5 studies showed that HbA1c level was significantly lower in the SGLT2i group (mean difference (MD) = -0.11, 95% CI (-0.18 to -0.05) , p = 0.0008). In the 3 studies evaluating bone density, BMD change was significantly higher in the SGLT2i group (standardized MD = 0.69, 95% CI (0.45 - 0.93), p < 0.00001). Based on the 2 studies reporting fracture events, the incidence rate was lower in the SGLT2i group (risk ratio (RR) = 0.09, 95% CI (0.02 - 0.47), p = 0.004). CONCLUSION: Preliminary evidence suggests that SGLT2i may be associated with modest improvements in BMD and no signal of increased fracture risk in patients with T2DM and osteoporosis. These findings remain to be confirmed in larger and longer-term randomized controlled trials.