. (2016). Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials. Diabetes, Obesity and Metabolism, 18(12), 1199-1206. https://doi.org/10.1111/dom.12742 2 Abstract Aim: Given the conflicting evidence of sodium-glucose cotransporter 2 (SGLT2) inhibitors on bone health in patients with type 2 diabetes Mellitus (T2DM), we aimed to evaluate the comparative effects of SGLT2 inhibitors on risk of bone fracture.Methods: PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov were systematically searched from inception to January 27, 2016 to identify RCTs reporting the outcome of fracture in T2DM patients with the use of SGLT2 inhibitors. A pairwise and network meta-analyses, as well as a cumulative meta-analysis were performed to calculate their odds ratios (ORs) and 95% confidence intervals (CIs).Results: A total of 38 eligible RCTs (10 canagliflozin, 15 dapagliflozin, and 13 empagliflozin) involving 30,384 patients with periods of follow-up ranged from 24 to 160 weeks were included. The fracture event rates were 1.59% in the SGLT2 inhibitor groups and 1.56% in the control groups. The incidence of fracture event was similar among these three SGLT2 inhibitor groups. Compared with placebo, canagliflozin (OR, 1.15; 95%CI, 0.71 to 1.88), dapagliflozin (OR, 0.68; 95%CI, 0.37 to 1.25), and empagliflozin (OR, 0.93; 95%CI, 0.74 to 1.18) was not significantly associated with an increased risk of fracture. Our cumulative meta-analysis indicated the robustness of our null findings of SGLT2 inhibitors. Conclusions:Our meta-analysis based on available RCT data does not support the harm effect of SGLT2 inhibitors on fracture, although future safety monitoring from RCT and real-world data with detailed information on bone health is warranted.