Article Text
PDF
Abstract
Introduction Type 2 diabetes is a risk factor for dementia and Parkinson’s disease (PD). Drug treatments for diabetes, such as metformin, could be used as novel treatments for these neurological conditions. Using electronic health records from the USA (OPTUM EHR) we aimed to assess the association of metformin with all-cause dementia, dementia subtypes and PD compared with sulfonylureas.
Research design and methods A new user comparator study design was conducted in patients ≥50 years old with diabetes who were new users of metformin or sulfonylureas between 2006 and 2018. Primary outcomes were all-cause dementia and PD. Secondary outcomes were Alzheimer’s disease (AD), vascular dementia (VD) and mild cognitive impairment (MCI). Cox proportional hazards models with inverse probability of treatment weighting (IPTW) were used to estimate the HRs. Subanalyses included stratification by age, race, renal function, and glycemic control.
Results We identified 96 140 and 16 451 new users of metformin and sulfonylureas, respectively. Mean age was 66.4±8.2 years (48% male, 83% Caucasian). Over the 5-year follow-up, 3207 patients developed all-cause dementia (2256 (2.3%) metformin, 951 (5.8%) sulfonylurea users) and 760 patients developed PD (625 (0.7%) metformin, 135 (0.8%) sulfonylurea users). After IPTW, HRs for all-cause dementia and PD were 0.80 (95% CI 0.73 to 0.88) and 1.00 (95% CI 0.79 to 1.28). HRs for AD, VD and MCI were 0.81 (0.70–0.94), 0.79 (0.63–1.00) and 0.91 (0.79–1.04). Stronger associations were observed in patients who were younger (<75 years old), Caucasian, and with moderate renal function.
Conclusions Metformin users compared with sulfonylurea users were associated with a lower risk of all-cause dementia, AD and VD but not with PD or MCI. Age and renal function modified risk reduction. Our findings support the hypothesis that metformin provides more neuroprotection for dementia than sulfonylureas but not for PD, but further work is required to assess causality.
- Diabetes Mellitus, Type 2
- Dementia
- Neurology
- Alzheimer Disease
Data availability statement
Data may be obtained from a third party and are not publicly available. Data may be obtained from a third party (OPTUM EHR) and are not publicly available.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
Data availability statement
Data may be obtained from a third party and are not publicly available. Data may be obtained from a third party (OPTUM EHR) and are not publicly available.
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors DN designed the study with input from LJL, QSL and YM. MF carried out the data curation and DN carried out all the analyses. DN wrote the manuscript with input from all authors. All authors reviewed the final manuscript and gave consent for publication. DN (the guarantor) accepts full responsibility for the finished work and/or the conduct of the study, had access to the data, and controlled the decision to publish.
Funding This work was supported by Janssen Pharmaceuticals. LJL is supported by the National Institute on Aging Intramural Research Program, USA. Additional funds were provided by Rosetrees Trust (M937) and John Black Charitable Fund (ID A2926).
Disclaimer The funding sources have no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Competing interests AJN-H has received funding from Janssen Pharmaceuticals, GlaxoSmithKline and Ono Pharma. QSL is an employee of Janssen Research & Development, Johnson & Johnson, and may hold equity in Johnson & Johnson.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.