Correlation between sodium-glucose co-transporter protein 2 inhibitors and fracture risk in patients with type 2 diabetes mellitus: a Meta-analysis

Abstract

Objective To systematically evaluate the correlation between sodium-glucose co-tran-sporter 2 (SGLT2) inhibitors and fracture risk in type 2 diabetes mellitus (T2DM) patients. Methods The related databases were searched. The randomized controlled trials (RCTs) which the outcome index included fracture in T2DM patients treated with SGLT2 inhibitors from the inception to August 2017 were enrolled into the study. The documents were selected according to the inclusion and exclusion criteria. After the data extraction and evaluation of methodological quality of RCTs, Meta-analysis was conducted using Rev Man 5.3 software. Results A total of 12 RCTs involving 28 181 patients were entered, including 17 747 patients in the test group (SGLT2 inhibitors) and 10 434 in the control group. The drugs used in the test group were canagliflozin (7 RCTs) and empagliflozin (5 RCTs). The drugs used in the control group were non-SGLT2 inhibitors including metformin, glimetazide and/or placebo. The results of Meta-analysis showed that the incidence of fractures in the test group was significantly higher than that in the control group[5.05% (897/17 747) vs. 4.40% (459/10 434), RR=1.27, 95%CI: 1.14-1.42, P<0.01]. Subgroup analysis showed that the incidence of fractures in the canagliflozin group was significantly higher than that in the control group [6.21% (679/10 938) vs. 5.28% (365/6 913), RR=1.31, 95%CI: 1.15-1.48, P<0.01]. There were no significant differences in the incidence of fractures between the empagliflozin group and the control group [3.20% (218/6 809) vs. 2.67% (94/3 521), RR=1.44, 95%CI: 0.35-5.90, P=0.61]. Conclusions Canagliflozin (a kind of SGLT2 inhibitors) can increase the incidence of fractures. It is suggested that the risk assessment should be done before medication for the benefit of patients. Key words: Sodium-glucose tranxpert 2; Fracture; Diabetes mellitus, type 2; Meta-analysis