(211) Agomelatine and Inverse Risk of Hypertension, Diabetes and Hyperlipidemia: A Nationwide Active-comparator Study

Background: Agomelatine is a novel antidepressant with structural similarities to melatonin. Prior research has highlighted the potential advantages of nighttime melatonin administration in diminishing daytime blood pressure among individuals with hypertension. Additionally, studies in mice have suggested that agomelatine can reduce circulating triglyceride levels and offer benefits for diabetes management. These findings suggested the possibility that agomelatine could positively impact metabolic disorders. Despite these promising indications, the actual effects of agomelatine on hypertension, diabetes, and hyperlipidemia in human populations remain uncertain.

Objectives: To evaluate the risk of hypertension, diabetes, and hyperlipidemia among agomelatine users.

Methods: This nationwide cohort study employed data sourced from the Taiwan National Health Insurance system. 74,147 agomelatine new users were defined as the study group and 22,815 fluoxetine new users were identified as the active comparator group. Primary outcome was the incidence of hypertension, diabetes, and hyperlipidemia during the 5-year follow-up period. The study employing an active-comparator design with a propensity score weighting strategy aimed at balancing baseline characteristics and comorbidities between the two groups. The sensitivity analysis and subgroup analyses were also performed. Using a stricter definition in the sensitivity analysis, hypertension, diabetes, and hyperlipidemia will be defined only if ≥ 3 diagnoses. The statistical analysis utilized the Cox proportional hazards model, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses in this study were carried out using the SAS statistical package.

Results: After adjusting for confounders, agomelatine demonstrated a significantly protective effect against hypertension (HR=0.85, 95% CI=0.81-0.899), diabetes (HR=0.91, 95% CI=0.86-0.96), and hyperlipidemia (HR=0.95, 95% CI=0.92-0.98). Notably, in the sensitivity analysis, agomelatine users had a lower hypertension incidence than fluoxetine users. The study findings remain robust after IPTW adjustments. Additionally, in women population, agomelatine users had a more noticeable decrease in the occurrence of hypertension then fluoxetine users (IPTW HR= 0.81, 95% CI= 0.77-0.85). This effect is not as observed within the men population.

Conclusions: Agomelatine demonstrates a notable protective effect in managing hypertension, diabetes, and hyperlipidemia, especially when compared to fluoxetine, with a pronounced effect on hypertension. These findings were consistently validated in sensitivity analyses.