Date Published: February 01, 2019
Publisher: JKL International LLC
Author(s): Tseng Chin-Hsiao.
This retrospective cohort study investigated dementia risk associated with metformin use in type 2 diabetes patients by using the reimbursement database of the Taiwan’s National Health Insurance. The patients had new-onset diabetes during 1999-2005 and were followed up until December 31, 2011. An unmatched cohort of 147,729 ever users and 15,676 never users of metformin were identified, and a matched-pair cohort of 15,676 ever users and 15,676 never users was created by propensity score (PS). Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using PS. Results showed that in the unmatched cohort, 713 never users and 3943 ever users developed dementia with respective incidence of 1029.20 and 570.03 per 100,000 person-years. The overall hazard ratio was 0.550 (95% confidence interval: 0.508-0.596). The hazard ratio for the first (<27.0 months), second (27.0-58.1 months) and third (>58.1 months) tertile of cumulative duration of metformin therapy was 0.975 (0.893-1.066), 0.554 (0.506-0.607) and 0.286 (0.259-0.315), respectively. Analyses in the matched cohort showed an overall hazard ratio of 0.707 (0.632-0.791) and the hazard ratio for the respective tertile was 1.279 (1.100-1.488), 0.704 (0.598-0.829) and 0.387 (0.320-0.468). In conclusion, metformin use is associated with a reduced dementia risk.
The National Health Insurance (NHI) was implemented in Taiwan since March 1995. It is a unique healthcare system that covers 99.6% of the Taiwan’s population and has contracts with all in-hospitals and 93% of all medical settings . All records including disease diagnoses, prescribed medications and performed procedures are kept as a database, which can be used for academic research after approval by ethics review. The present study was granted an approval number 99274.
Table 1 compares the characteristics between never and ever users of metformin. In the unmatched original cohort, age and sex differed significantly. The mean age was older (63.4±10.4 vs. 61.6±10.0 years, P<0.01) and the proportion of men was higher (57.47% vs. 54.24%, P<0.01) in never users. All other variables, except hypertension, sulfonylureas, pioglitazone and head injury, also differed significantly in the original cohort. However, in the matched cohort, age and sex were similar and most variables were not different significantly (except for eye diseases, insulin, sulfonylureas, alcohol-related diagnoses and fibrate). While examining the standardized differences in the matched cohort, none had a value >10%.
The findings suggested that metformin use in type 2 diabetes patients was associated with a significantly lower risk of dementia, especially when it had been used for more than 2 years (Table 2). The risk reduction showed a dose-response pattern and was consistent in sensitivity analyses (Table 3). The lower risk of dementia associated with metformin use was not affected by the year of enrollment (Table 4).