Introduction and Objective: Alpha-lipoic acid (ALA) is used for diabetic neuropathy, but their potential impact on macrovascular complications remains unclear. This study aimed to investigate the association between ALA use and the risk of cardiovascular outcomes and mortalityMethods: We conducted a retrospective cohort study using the Korean National Health Insurance Service Health Screening Cohort. Participants aged 40-79 who were diagnosed with diabetic neuropathy from 2011 to 2015 were followed up to December, 2019. ALA users were defined as those prescribed ALA for ≥6 months. Propensity score matching was performed to balance baseline characteristics, and Cox proportional hazards models were used to evaluate associations between ALA use and myocardial infarction (MI), stroke, diabetic foot ulcers (DFU), amputation, and all-cause mortality.Results: A total of 8,740 participants (4,370 ALA users and 4,370 non-users) were included after matching. Over a median follow-up of 8 years, ALA use was significantly associated with a lower risk of MI (Hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.74-0.98) and all-cause mortality (HR 0.82, 95% CI 0.72-0.93), while no significant associations were observed for stroke, diabetic foot ulcer, or amputation. Subgroup analyses revealed a pronounced MI risk reduction in individuals with high comorbidity index (HR 0.38, 95% CI 0.22-0.65). In a ‘user-only design’ analysis, longer use of ALA (>2 years) was associated with a stronger MI risk reduction (HR 0.48, 95% CI 0.40-0.59, p for trend < 0.001).Conclusion: ALA use, particularly long-term use, was associated with a reduced risk of MI and all-cause mortality in individuals with diabetic neuropathy. These findings highlight the potential role of antioxidant as adjuncts in managing macrovascular complications in diabetes.
S. Kim: None. Y. Cho: None. H. Park: None. D. Seo: None. S. Hong: None.
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