Aspirin lowers diabetes risk during COVID-19, but not without side effects

New research suggests that taking a daily aspirin may halve your risk of developing diabetes, especially during the COVID-19 pandemic, by targeting inflammation, but not without trade-offs.

Study: Aspirin reduces the risk of type 2 diabetes associated with COVID-19. Image Credit: Studio Romantic / ShutterstockStudy: Aspirin reduces the risk of type 2 diabetes associated with COVID-19. Image Credit: Studio Romantic / Shutterstock

In a recent study published in the journal npj Metabolic Health and Disease, a group of researchers assessed whether daily low-dose aspirin reduces the risk of new-onset type 2 diabetes (T2D) associated with Coronavirus Disease 2019 (COVID-19).

Background

T2D affects over 500 million people globally, and its incidence sharply increased during the COVID-19 pandemic. Several factors, including stress, poor dietary habits, reduced physical activity, and limited access to healthcare, may have contributed to this rise in cases.

Experimental research suggests that inflammation plays a key role in disrupting insulin function, prompting interest in anti-inflammatory treatments for prevention. Aspirin has anti-inflammatory effects that may help regulate blood sugar levels, in addition to its cardiovascular benefits. However, most of the findings so far come from controlled trials in older adults, and to understand how aspirin affects T2D in everyday life, further research is needed.

About the study

The present longitudinal cohort study was conducted using electronic health records from Cooperative of General Practitioners (COMEGEN)- a healthcare network under the Italian Ministry of Health operating in Naples. The COMEGEN database contains clinical information on over 200,000 adults. Researchers collected data from January 1, 2018, to December 31, 2022, among adults aged 18 years and older. Adults were eligible if they had neither a previous diagnosis of T2D, chronic kidney disease, or cardiovascular events, nor used aspirin before 2018.

The primary exposure was initiation of daily low-dose aspirin therapy (100 mg), and the primary outcome was a new diagnosis of T2D, confirmed by diagnostic codes and prescriptions. Researchers confirmed COVID-19 infections using reverse transcription polymerase chain reaction (RT-PCR) test data from the Campania Region’s official registry.

To ensure accurate comparisons between aspirin users and non-users, the researchers matched participants based on factors such as age, sex, body mass index (BMI), prediabetes status, and use of blood pressure or lipid-lowering medications. They used Cox regression to track the time until new diabetes cases appeared and plotted overall risk trends with Kaplan-Meier curves. Bleeding events were monitored throughout the study and classified as major, moderate, or minor.

The study design also allowed for the reliable capture of lesser-severity bleeding episodes, which are often missed in clinical trials but can significantly impact patients. All results were considered statistically significant if p-values were less than 0.05, and the analysis was performed using R software (version 4.4.0).

Study results

Out of 247,975 eligible individuals in the COMEGEN database, 35,525 met inclusion criteria. After applying 1:1 propensity score matching, 4,139 individuals who received low-dose aspirin were compared with an equal number of matched non-users. The matched groups were similar in age, gender, BMI, and baseline comorbidities, ensuring reliable comparisons.

Over the observation period, 999 new cases of T2D were reported. Among aspirin users, the incidence rate was 15.9 per 1,000 person-years, while in the control group, it was 32 per 1,000 person-years. Cox regression analysis revealed that aspirin therapy was associated with a 52% reduction in the risk of T2D (hazard ratio [HR] = 0.48; 95% confidence interval [CI]: 0.42--0.45; p < 0.001). Kaplan-Meier curves confirmed that the divergence in T2D risk became significant after the second year of aspirin use and continued to widen over time.

When the data were split into pre-pandemic and COVID-19 pandemic periods, the protective effect remained strong. Prior to COVID-19, aspirin users had a 29% reduced risk of developing T2D (HR = 0.71; 95% CI: 0.56-0.89). During the COVID-19 period, the risk reduction increased to 62% (HR = 0.38; 95% CI: 0.32-0.35). Kaplan-Meier analysis revealed an earlier and more pronounced separation of risk curves during the pandemic, suggesting that aspirin’s anti-inflammatory properties had increased relevance amid COVID-19-related immune activation.

The safety analysis included 8,278 participants equally divided between aspirin users and non-users. Major bleeding events occurred in 0.3% of aspirin users, compared to 0.1% in the control group. Moderate bleeding rates were 8.3 vs 4.2 events per 1,000 person-years, and minor bleeding, including hematuria, was slightly more common in the aspirin group (6.7 vs 4.9 per 1,000 person-years). While aspirin did raise bleeding risks, the rates were consistent with prior studies, and most events were not life-threatening.

These findings suggest that low-dose aspirin significantly reduces the risk of new-onset type 2 diabetes, particularly during the COVID-19 pandemic. This effect highlights the inflammatory basis of diabetes pathogenesis in the context of viral infection, supporting further exploration of targeted anti-inflammatory strategies in high-risk populations.

Conclusions

To summarize, this real-world cohort study using COMEGEN data demonstrates that daily low-dose aspirin significantly reduces the incidence of type 2 diabetes (T2D), particularly during the COVID-19 pandemic. The results strengthen the hypothesis that inflammation is a key driver of COVID-19-related metabolic disturbances and demonstrate aspirin’s potential in reducing this risk. However, the associated increase in bleeding events warrants caution and individualized risk-benefit evaluation.

While the study is robust, the authors acknowledge limitations, including the lack of data on inflammatory markers, lifestyle changes, and COVID-19 vaccination status. These findings should not lead to the widespread use of aspirin for diabetes prevention, but rather suggest promising therapeutic directions.

Journal reference:
Vijay Kumar Malesu

Written by

Vijay Kumar Malesu

Vijay holds a Ph.D. in Biotechnology and possesses a deep passion for microbiology. His academic journey has allowed him to delve deeper into understanding the intricate world of microorganisms. Through his research and studies, he has gained expertise in various aspects of microbiology, which includes microbial genetics, microbial physiology, and microbial ecology. Vijay has six years of scientific research experience at renowned research institutes such as the Indian Council for Agricultural Research and KIIT University. He has worked on diverse projects in microbiology, biopolymers, and drug delivery. His contributions to these areas have provided him with a comprehensive understanding of the subject matter and the ability to tackle complex research challenges.    

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