Risk factors for bone fractures in type 2 diabetes and the impact of once-weekly exenatide: Insights from an EXSCEL post-hoc analysis

We investigated bone fracture predictors in people with T2D enrolled in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) and evaluated the effects of once-weekly exenatide (EQW) on incident bone fractures. EXSCEL randomised 14,752 people to EQW 2 mg or placebo with a median follow-up of 3.2 years. In this post-hoc analysis, baseline features associated with incident bone fractures were evaluated with multivariable Cox proportional hazard regression models, accounting for age and sex as confounders. Incidence rates were compared between study arms, and time-to-event analyses performed using Cox-proportional hazard models. The primary outcome occurred in 168 (1.1 %) participants. The presence of neuropathy at baseline was associated with a 50 % higher risk (hazard ratio [HR] 1.50, 95 % confidence interval [CI] 1.10-2.05, P = 0.010) of incident bone fractures, while taking metformin at baseline was associated with a 47 % lower risk (HR 0.53, 95 %CI 0.39-0.73, P < 0.001). Incidence rates of bone fractures were similar in the EQW group and in the placebo group (HR 1.11, 95 %CI 0.82-1.51, P = 0.49). Bone fractures in people with T2D occur more frequently in those with diabetic neuropathy, but less frequently in those taking metformin. No evidence was seen of any impact of EQW treatment on bone fractures.