Aspirin reduces the risk of type 2 diabetes associated with COVID-19
Valentina Trimarco, Raffaele Izzo, Daniela Pacella, Maria Virginia Manzi, Stanislovas S Jankauskas, Paola Gallo, Francesco Rozza, Giuseppe Giugliano, Alessandra Spinelli, Giovanni Esposito, Roberto Piccinocchi, Gaetano Piccinocchi, Carmine Morisco, Maria Lembo, Gaetano Santulli, Bruno Trimarco
npj Metabolic Health and Disease, doi:10.1038/s44324-025-00072-3
This study aimed to determine whether daily low-dose aspirin reduces the risk of type 2 diabetes (T2D) associated with COVID-19. A longitudinal cohort of 200,000 adults followed from 2018 to 2022 was analyzed, comparing T2D incidence between aspirin users and non-users. Propensity score matching was used to balance the groups. The incidence of T2D was substantially lower in the aspirin group, with Cox regression showing a 52% risk reduction. Kaplan-Meier analysis confirmed a significant divergence in cumulative T2D risk after two years. This protective effect was observed both before and during the COVID-19 pandemic, with a stronger association during the pandemic period. These findings indicate that daily low-dose aspirin significantly reduces the risk of COVID-19-associated new-onset T2D, highlighting the role of inflammation in the pathogenesis of T2D triggered or unmasked by COVID-19. Substantial evidence has shown that the incidence of type 2 diabetes (T2D) increased during the acute phase of COVID-19 pandemic [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] . Initial reports compared groups of patients who certainly had a positive SARS-CoV-2 test vs individuals with similar demographic characteristics who did not have COVID-19, showing the effect of the long-term individual COVID-19 infection (post-acute sequelae) on the incidence of diabetes [reviewed in ref. 3]. Recently, we analyzed a large real-world dataset of adults and demonstrated that the incidence of newly diagnosed T2D in the general population was 4.85 per 1000 person-years before the COVID-19 pandemic, vs 12.21 per 1000 person-years during the pandemic 14 . However, these findings do not allow any conclusion on the pathophysiologic mechanisms underlying the increased incidence of T2D in the pandemic period, which could be ascribed to direct effects of SARS-CoV-2 infection, and indirect effects like stress, changes in diet/exercise and in cardiovascular prevention strategies, as well as reduced access to healthcare [15] [16] [17] [18] . The observation that fully vaccinated individuals might be protected from the risk of incident diabetes following SARS-CoV-2 infection 19 seems to support a functional role of inflammation, autoimmune dysregulation, and endothelial dysfunction in the regulation of this process [20] [21] [22] [23] [24] [25] [26] [27] [28] . Indeed, experimental and epidemiological data have suggested that subclinical inflammation might contribute to metabolic diseases, insulin resistance, and T2D 29, 30 . Specifically, analyzing the comprehensive data collected in the ASPREE trial 31 , Zoungas and coworkers 32 have tested the hypothesis that treatment of healthy elder adults with 100 mg daily of enteric-coated oral aspirin would reduce incident diabetes or slow the increase in fasting glucose plasma concentration over time when compared with treatment with placebo. This post hoc analysis 32 revealed that, during a median follow-up of 4,7 years, the..
Author contributions G.S. and B.T. conceived the idea; V.T., R.I., M.V.M., and B.T. wrote the first draft of the paper; D.P. performed statistical analysis; S.S.J., P.G., F.R., G.G., A.S., G.E., R.P., G.P., C.M., and M.L. helped in collecting and analyzing data; G.S. revised critically the paper. V.T., R.I., D.P., and M.V.M. are co-first authors; G.S. and B.T. are co-last authors.
Competing interests The authors declare no competing interests.
Additional information Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s44324-025-00072-3 . Correspondence and requests for materials should be addressed to Gaetano Santulli. Reprints and permissions information is available at http://www.nature.com/reprints Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article..
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