Abstract
Aims To 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.
Methods This 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 1st and 31st December 2009. The follow-up was until 31st December 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.
Results A 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.
Conclusion Metformin 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.
Highlights
Patients with type 2 diabetes have an increased risk of cognitive, anxiety or depressive problems
Metformin use was associated with lower risks of new diagnosis of dementia, anxiety disorder and depression
Patients who developed dementia had lower levels of albumin, alanine transaminase and HbA1c compared to those who developed anxiety disorder and depression
Appropriate glycemic control and maintenance of normal liver function are important in slowing cognitive decline in type 2 diabetes mellitus
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This study did not receive any funding
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster and the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee.
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Yes
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Footnotes
↵* Co-first authors.
Data Availability
All data produced in the present study are available upon reasonable request to the authors