Abstract
BACKGROUND: Prediabetes represents the final stage on the glycemic spectrum before the onset of type 2 diabetes mellitus (T2DM), and delaying its progression offers a unique opportunity to address the growing T2DM epidemic. METHODS: In this longitudinal cohort study, we investigated the effect of daily low-dose aspirin on the development of T2DM in individuals with prediabetes residing in Naples, Italy, who were followed by their primary care physicians between 2018 and 2022. Outcomes in the aspirin-treated group were compared with those in a control group not receiving aspirin, using data from the same database. Propensity score matching was employed to ensure comparability of covariates at baseline. RESULTS: The primary outcome was the onset of T2DM, defined as a new diagnosis accompanied by antidiabetic prescriptions lasting more than 30 days. Gastrointestinal bleeding was assessed as the safety endpoint. Over the follow-up period, 488 new cases of T2DM were documented (15.6% of the total population), with 174 cases occurring in the aspirin group (22.3 per 1000 person-years) and 314 in the non-aspirin group (40.2 per 1000 person-years), indicating a significantly lower incidence of diabetes among aspirin-treated individuals. Given the difference in comorbidity rates between groups, a Cox regression analysis was conducted across the entire follow-up period, showing that aspirin use was associated with a 47% reduction in the risk of developing T2DM (HR 0.53, 95% CI 0.44–0.64, p < 0.001). However, aspirin use was also linked to an increased risk of gastrointestinal bleeding (4.9% vs 3.1%, p < 0.05). Kaplan–Meier survival curves confirmed a significantly lower cumulative incidence of T2DM in the aspirin-treated group (log-rank test p < 0.0001). CONCLUSIONS: Daily treatment with 100 mg aspirin was associated with approximately a 50% reduction in the incidence of new-onset T2DM, but also with an increased risk of gastrointestinal bleeding, in elderly individuals with prediabetes. GRAPHICAL ABSTRACT: [Image: see text]