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Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis
Allie Seminer1, Alfredi Mulihano1, Clare O'Brien2
1HRB Clinical Research Facility, University of Galway, Galway, Ireland.
JAMA Neurology
|April 7, 2025
Summary
Cardioprotective glucose-lowering therapies did not overall reduce dementia risk. However, glucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly lowered dementia incidence in this meta-analysis.
Area of Science:
- Endocrinology and Neurology
- Pharmacology and Therapeutics
Background:
- Diabetes is a known risk factor for dementia, but the efficacy of glucose-lowering treatments in preventing cognitive decline remains unclear.
- Investigating the role of specific cardioprotective glucose-lowering therapies in dementia prevention is crucial for patient care.
Purpose of the Study:
- To evaluate whether cardioprotective glucose-lowering therapies (SGLT2is, GLP-1RAs, metformin, pioglitazone) reduce the risk of dementia or cognitive impairment.
- To analyze the association with primary dementia subtypes and cognitive score changes.
Main Methods:
- A systematic search of PubMed and Embase databases was conducted up to July 11, 2024.
- Included randomized clinical trials comparing cardioprotective glucose-lowering therapies with controls, focusing on dementia incidence or cognitive changes.
- Random-effects meta-analysis was employed to pool treatment effects, adhering to PRISMA guidelines.
Main Results:
- Twenty-six trials with 164,531 participants were analyzed. Overall, cardioprotective glucose-lowering therapy showed no significant association with reduced dementia risk (OR, 0.83 [95% CI, 0.60-1.14]).
- Glucagon-like peptide-1 receptor agonists (GLP-1RAs) demonstrated a statistically significant reduction in dementia risk (OR, 0.55 [95% CI, 0.35-0.86]).
- Sodium-glucose cotransporter-2 inhibitors (SGLT2is) did not show a significant association with reduced dementia risk (OR, 1.20 [95% CI, 0.67-2.17]).
Conclusions:
- While not universally effective, specific glucose-lowering agents show promise in dementia prevention.
- Glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent a potential therapeutic strategy for reducing dementia incidence in diabetic patients.
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