Patients with type 2 diabetes have a higher risk of developing dementia. There are few studies that have addressed whether anti-diabetic treatments have effects on the risk of developing dementia among patients with type 2 diabetes.
Sodium glucose co-transporter (SGLT)-2 inhibitors are the newest agents available to treat type 2 diabetes. Clinical studies also found that SGLT-2 inhibitor use decreases cardiovascular disease. The vascular protection from SGLT-2 inhibitors may potentially decrease the risk of dementia among patients with type 2 diabetes.
This will be the first study to determine whether SGLT-2 inhibitor use decreases the risk of dementia among patients with type 2 diabetes. We will use a large population database in the United Kingdom with robust statistical methods to address this clinical question.
The findings of our study will inform the clinical community of whether SGLT-2 inhibitor use should be preferably prescribed to patients with a higher risk of developing dementia, such as the elderly.
1) Cognitive dysfunction and eventual development of dementia is increasingly being recognized as a complication associated with type 2 diabetes. Sodium glucose co-transporter (SGLT)-2 inhibitors are used in the treatment of type 2 diabetes and have been shown to have beneficial effects beyond glycemic control. RCTs have demonstrated that SGLT-2 inhibitors use leads to a significantly decreased risk of adverse cardiovascular events, renal outcomes and mortality. Findings from animal studies suggest that SGLT-2 inhibitors have neuroprotective effects primarily mediated by anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms. Since SGLT-2 inhibitors may play a role in conferring vascular protection and have been shown to affect brain metabolism, the use of these antidiabetic agents may decrease the risk of dementia among individuals with type 2 diabetes.
We will use the Clinical Practice Research Database Aurum to conduct a population-based cohort study. We will assemble a cohort of individuals with type 2 diabetes between 2013 and 2021, followed until December 31, 2022. Cox proportional hazards models with propensity score fine stratification weighting will be used to estimate the adjusted hazard ratios and corresponding 95% confidence interval of incident dementia among SGLT-2 inhibitor users versus dipeptidyl-peptidase-4 inhibitor users. We will also conduct several sensitivity analyses, including a Fine and Gray analysis to account for competing risks to confirm our findings.
Given that SGLT-2 inhibitors have effects in metabolic and vascular related pathways involved in the pathogenesis of dementia, this study will address whether SGLT-2 inhibitor use is associated with a decreased risk of dementia among individuals with type 2 diabetes. If SGLT-2 inhibitor use is associated with a decreased risk of dementia, this finding will justify and guide the design of future RCTs in assessing SGLT-2 inhibitor use and cognitive outcomes among individuals with type 2 diabetes.
The primary outcome of this study will be incident dementia.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Oriana Hoi Yun Yu - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Chenjie Xia - Collaborator - McGill University
Christel Renoux - Collaborator - McGill University
Laurent Azoulay - Collaborator - McGill University
Robert Platt - Collaborator - McGill University
Ying Cui - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Zarin Abdullah - Collaborator - McGill University
Banruo Li - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Zarin Abdullah - Collaborator - McGill University
Practice Level Index of Multiple Deprivation