Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis

Aims: Diabetes is associated with increased risk of fracture. This study aims to evaluate the correlation between anti-diabetic agents and fracture risk in patients with type 2 diabetes.Methods: Literature research was conducted using PubMed, Embase, and ClinicalTrials.gov. Search-term included type 2 diabetes, fracture, randomized controlled trial, and seven kinds of anti-diabetic agents. Random -effect models established fractures in the follow-up period as the primary outcome. A network meta-analysis was performed to compare available treatments within a single Bayesian analytical framework.Results: A total of 191,361 patients were included in 161 studies, with 2916 fractures. DPP-4i (risk ratio [RR] 1.76 [95 % confidence interval (CI) 1.21-2.55]), SGLT-2i (RR 1.5 [95 % CI 1.05-2.16]) and placebo (RR 1.44 [95 % CI 1.04-1.98]) increased fracture risk when compared to GLP1-RA. GLP1-RA (RR 0.5 [95 % CI 0.31-0.79]) and SU (RR 0.56 [95 % CI 0.41-0.77]) provided greater protection against fracture than TZD. DPP-4i increased fracture risk when compared to SU (RR 1.55 [95 % CI 1.08-2.22]), and was comparable in effect to TZD.Conclusions: GLP1-RA offered better protection against fracture than placebo. Insulin and SU had effects com-parable with GLP1-RA. SU offered greater protection against fractures than TZD and DPP-4i. SGLT-2i increased risk of fracture when compared to GLP1-RA.

Automated summary

This study found that SGLT-2i, DPP-4i, and placebo are associated with increased risk of fracture, while GLP1-RA and SU provide better protection against fractures. Compared to TZD, GLP1-RA and SU offer better protection against fractures, while DPP-4i has a relatively increased risk of fracture.