Daily low-dose aspirin and incident type 2 diabetes in community-dwelling healthy older adults: a post-hoc analysis of efficacy and safety in the ASPREE randomised placebo-controlled trial

Background Inflammation has been implicated in the pathogenesis of diabetes. This study investigated the randomised treatment effect of low-dose aspirin on incident type 2 diabetes and fasting plasma glucose (FPG) concentrations among older adults. Methods ASPREE was a double-blind, placebo-controlled trial of daily oral low-dose aspirin. The study population included community-dwelling individuals aged 70 years or older (>= 65 years for US minority ethnic groups) in the USA and Australia who were free of cardiovascular disease, independence-limiting physical disability, or dementia. For the post-hoc analysis, we excluded participants with diabetes at baseline or with incomplete or missing incident diabetes data during follow-up. Participants were randomly assigned 1:1 to oral 100 mg daily enteric-coated aspirin or placebo. Incident diabetes was defined as self-reported diabetes, commencement of glucose-lowering medication, or a FPG concentration of 7 center dot 0 mmol/L or more assessed at annual follow-up visits among participants with no diabetes at baseline. We used Cox proportional hazards models and mixed-model repeated measures to assess the effect of aspirin on incident diabetes and FPG concentrations in the intention-to-treat population. We assessed major bleeding in participants who had taken at least one dose of study medication. Findings Between March 10, 2010, and Dec 24, 2014, a total of 16 209 participants were included (8086 [49 center dot 9%] randomly assigned to aspirin and 8123 [50 center dot 1%] randomly assigned to placebo). During a median follow-up of 4 center dot 7 years (IQR 3 center dot 6-5 center dot 7), 995 (in 6 center dot 1% individuals) incident cases of type 2 diabetes were recorded (459 in the aspirin group and 536 in the placebo group). Compared with placebo, the aspirin group had a 15% reduction in risk of incident diabetes (hazard ratio 0 center dot 85 [95% CI 0 center dot 75 to 0 center dot 97]; p=0 center dot 013) and a slower rate of increase in FPG concentration at year 5 (between-group difference estimate -0 center dot 048 mmol/L [95% CI -0 center dot 079 to -0 center dot 018]; p=0 center dot 0017). Major bleeding (major gastrointestinal bleeding, intracranial bleeding, and clinically significant bleeding at other sites) occurred in 510 (3 center dot 2%) of 16 104 participants (300 [3 center dot 7%] in the aspirin group and 210 [2 center dot 6%] in the placebo group). Compared with placebo, the aspirin group had a 44% increase in risk of major bleeding (hazard ratio 1 center dot 44 [95% CI 1 center dot 21 to 1 center dot 72]; p<0 center dot 0001). Interpretation Aspirin treatment reduced the incidence of type 2 diabetes and slowed the increase in FPG concentration but increased major bleeding among community-dwelling older adults. Given the increasing prevalence of type 2 diabetes among older adults, the potential for anti-inflammatory agents such as aspirin to prevent type 2 diabetes or improve glucose levels warrants further study with a comprehensive assessment of all potential safety events of interest.