Agomelatine and the potential inverse risk of metabolic disorders: a nationwide cohort study with an active comparator design in Taiwan.

BACKGROUND: Agomelatine, a melatonergic antidepressant, acts as a dual MT1/MT2 receptor agonist and a 5-HT2C receptor antagonist, effectively resynchronizing circadian rhythms while exerting antidepressant and anxiolytic properties. It is considered safe and may have anti-inflammatory, antioxidant, and blood pressure-lowering properties. However, its effects on hypertension, diabetes, and hyperlipidemia remain unclear. This study aimed to assess the association between agomelatine use and the impact on these metabolic conditions. METHODS: Using Taiwan’s National Health Insurance data, this nationwide cohort study compared 25,923 agomelatine users with 83,535 fluoxetine users. Outcomes included new-onset hypertension, diabetes, and hyperlipidemia over a 5-year follow-up. An active-comparator design with propensity score weighting balanced baseline characteristics. Cox proportional hazards models provided hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses were conducted using SAS. RESULTS: In the propensity score-weighted cohort over a 5-year follow-up, agomelatine users exhibited a significantly lower risk of hypertension compared to fluoxetine users (adjusted HR 0.802; 95% CI, 0.770–0.836). Consistent with this cardiovascular benefit, agomelatine use was also associated with reduced risks of incident diabetes mellitus (adjusted HR 0.875; 95% CI, 0.827–0.927) and hyperlipidemia (adjusted HR 0.938; 95% CI, 0.906–0.972) throughout the study period. Subgroup analyses showed generally consistent inverse associations for hypertension across various demographic and clinical strata. CONCLUSION: This nationwide cohort study demonstrates associations between agomelatine use and lower risks of hypertension, diabetes mellitus, and hyperlipidemia. These findings provide population-based evidence that may inform future research, although further studies are warranted to confirm these observations.