Effects Of Sodium Glucose Cotransporter-2 Inhibitors On The Risk Of Bone Fracture In Patients With Type 2 Diabetes: A Systematic Review

Aim:To evaluate the effects of sodium-glucose co-transporter 2(SGLT2)inhibitors on risk of bone fracture in patients with type 2 diabetes(T2DM).Methods:We searched for randomized controlled trials(RCTs)in PubMed,EMBASE,the Cochrane Library,ClinicalTrials.gov from inception to 31 December 2017 and collect clinical controlled trials according to selection criter.Quality assessment used the Cochrane Collaboration's tool for assessing risk of bias.Statistical analysis was conducted by the Revman5.3 software of Cochrane Collaboration.We will compare outcome measures for dichotomous(binary)data using relative risks(RR)with 95% confidence intervals(CI)and P value.Data without heterogeneity(p?0.1,I~2?50%)could be pooled using fixed effect model,and those with heterogeneity(p<0.1,I~2>50%)could be solved by subgroup analysis,sensitivity analysis as well as randomized effect model.Statistical significance was assumed at the P<0.05 level.Results: A total of 35 randomized,controlled trials(RCTs)(17 dapagliflozin,10 canagliflozin,8 empagliflozin)involving 26064 patients with type 2 diabetes mellitus were included in the analysis..The published language of included trials was English and follow-ups ranging from 12 weeks to 3.1 years.The results of systematic review showed that It is without statistical heterogeneity between SGLT2 inhibitors versus control(I~2=0%,P=0.64)?dapagliflozin(I~2=0%,P=0.79)?canagliflozin(I~2=9%,P=0.36)?empagliflozin(I~2 =26%,P=0.22).The pooled risk ratio of bone fracture in SGLT2 inhibitors groups and control groups was [P=0.2,M-H RR=0.88 95%CI(0.72,1.07),I~2 =0%].The pooled risk ratio for dapagliflozin,canagliflozin,empagliflozin was[P=0.77,M-H RR=0.92 95%CI(0.51,1.64),I~2 =0%],[P=0.41,M-H RR=0.8295%CI(0.52,1.31),I~2 =9%],[P=0.32,M-H RR=0.89 95%CI(0.71,1.12),I~2=26%],respectively.No significant difference was observed in the risk of bone fracture among treatment and control.Conclusion: Increase risk of bone fracture among SGLT2 inhibitors groups and control groups was not observed in our meta-analysis.For some limitations in thisdata,we expect that there will be more evidence provided by larger sample and longer duration RCTs to assess fracture risk of the SGLT2 inhibitors in T2 DM.