Metformin use is associated with lower risks of dementia, anxiety and depression: The Hong Kong Diabetes Study

Abstract

AbstractAimsTo compare the effects of metformin and sulphonylurea on new-onset dementia, anxiety disorder and depression, and all-cause mortality in patients with type 2 diabetes mellitus.MethodsThis is a retrospective population-based cohort study of type 2 diabetes mellitus patients exposed to either metformin or sulphonylureas attending the Hospital Authority of Hong Kong between 1stand 31stDecember 2009. The follow-up was until 31stDecember 2019. The primary outcome was a new diagnosis of dementia, and anxiety disorder/depression. Propensity score matching (1:1 ratio) between metformin and sulphonylurea users based on demographics, CAIDE score, CHA-DS-VASc score, Charlson comorbidity index, past comorbidities, medications, and total cholesterol was performed. Cox regression was used to identify significant risk predictors. Cause-specific and subdistribution hazard models were also used.ResultsA total of 89,711 patients (46% men, mean age: 67 years old [SD: 12]) followed-up for 1,579 days (SD: 650). Metformin users were at a lower risk of dementia (before: 0.78 [0.72, 0.84], P-value < 0.0001; after: 0.88 [0.80, 0.97], P-value = 0.0074), anxiety disorder and depression (before: 0.77 [0.69, 0.86], P-value < 0.0001; after: 0.71 [0.61, 0.82], P-value < 0.0001), and all-cause mortality (before: 0.69 [0.68, 0.71], P-value < 0.0001; after: 0.83 [0.80, 0.85], P-value < 0.0001). These associations remained significant in the competing risk models.ConclusionMetformin use is associated with lower risks of dementia, new-onset anxiety disorder and depression, and all-cause mortality, compared to sulphonylurea use. The protective effects of metformin and possible use in drug repurposing for indications beyond diabetes warrant further investigation.HighlightsPatients with type 2 diabetes have an increased risk of cognitive, anxiety or depressive problemsMetformin use was associated with lower risks of new diagnosis of dementia, anxiety disorder and depressionPatients who developed dementia had lower levels of albumin, alanine transaminase and HbA1c compared to those who developed anxiety disorder and depressionAppropriate glycemic control and maintenance of normal liver function are important in slowing cognitive decline in type 2 diabetes mellitus