medwireNews: Treatment with aspirin decreases the incidence of type 2 diabetes and attenuates the increase in fasting plasma glucose (FPG) levels among older adults but increases the risk for major bleeding, suggests a post-hoc analysis of the ASPREE trial.
“Given the increasing prevalence of diabetes around the world, the potential for anti-inflammatory agents such as aspirin to prevent or delay incident diabetes or improve glucose levels warrants further study,” the researchers say.
ASPREE is a double-blind, placebo-controlled trial conducted among community-dwelling individuals more than 70 years of age living in USA and Australia who were free from cardiovascular disease, independence-limiting physical disability, and dementia at baseline.
Sophia Zoungas (Monash University, Melbourne, Victoria, Australia) and colleagues report in The Lancet Diabetes & Endocrinology that aspirin, compared with placebo, lowered the risk for incident diabetes by 15% (12.7 vs 14.8 events per 1000 person–years) and decelerated the rate of FPG increase at 5 years (between-group difference –0.048 mmol/L (0.9 mg/dL)).
However, the risk for major gastrointestinal, intracranial, or clinically significant bleeding at other sites increased by a significant 44% in the participants given aspirin compared with the controls (3.7 vs 2.6%).
The post-hoc analysis assessed the effect of oral enteric-coated aspirin 100 mg/day or placebo on the occurrence of incident diabetes and safety in a group of 16,209 participants (57% women) over a median follow-up period of 4.7 years. Overall, 6.1% of participants experienced incident diabetes events, as determined by self-report of diabetes, use of glucose-lowering medication, or an increase in FPG levels above 7.0 mmol/L (126.0 mg/dL) recorded during annual testing.
Zoungas and researchers note that there was no significant difference in the effect of aspirin based on age, race, sex, BMI, country, statin use, previous use of aspirin, smoking, history of hypertension, frailty, or prediabetes.
The investigators state that “[g]iven the proposed role of chronic subclinical inflammation in the development of insulin resistance or deficiency, which can increase an individual’s susceptibility to glucometabolic disorders, it is important to further understand any effect of aspirin on incident diabetes using a contemporary cohort of older adults who can be at greater risk due to age alone.”
In a related commentary, John Ostrominski and Vanita Aroda (both from Harvard Medical School, Boston, Massachusetts, USA) observe that the benefit of aspirin in diabetes prevention is offset by the increase in major bleeding.
"As such, when considering the increased rate of all-cause death observed in the primary trial, these findings do not provide sufficient rationale for a change in routine practice," they write.
Nevertheless, Ostrominski and Aroda believe that the study “amplifies the need for vigilant diabetes screening and treatment across the lifespan” and supports “the potential role of inflammation-targeted strategies in primary diabetes."
They conclude that "[f]or aspirin, precision approaches might identify subpopulations that are likely to derive the maximal net cardiometabolic benefit (eg, those with the highest risk of incident diabetes and cardiovascular disease but the lowest risk of bleeding and progressive cancer).”
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Lancet Diabetes Endocrinol 2023; doi:10.1016/S2213-8587(23)00327-3
Lancet Diabetes Endocrinol 2023; doi:10.1016/S2213-8587(23)00363-7