Faculty mentor/PI email address
TGandrabura@virtua.org
Keywords
GLP-1 Agonist, Disease Prevention, Type 2 Diabetes
Date of Presentation
5-6-2026 12:00 AM
Poster Abstract
Background: GLP-1 receptor agonists improve glycemic and cardiovascular outcomes in type 2 diabetes mellitus (T2DM), but their impact on neurocognitive and neurological outcomes remains incompletely characterized. We evaluated the association between GLP-1 agonist use and incident cognitive impairment, neurodegeneration, and healthcare utilization in T2DM patients without baseline cognitive deficits.
Methods: A retrospective cohort study was conducted using the TriNetX Global Collaborative Network. Adults (≥40 years) with T2DM and no prior cognitive impairment, Alzheimer's disease, Parkinson's disease, multiple sclerosis, or cerebral infarction were identified. Cohort 1 received a GLP-1 agonist (semaglutide, tirzepatide, liraglutide, or dulaglutide) after T2DM diagnosis; Cohort 2 received no GLP-1 therapy. Propensity score matching (1:1) yielded 1,099,766 patients per cohort. Primary outcomes included mild cognitive impairment (MCI), Alzheimer's disease, and Parkinson's disease. Secondary outcomes included encephalopathy, falls/fractures, delirium/psychosis, inpatient admissions, and all-cause mortality. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals were estimated.
Results: GLP-1 use was associated with significantly lower risks of MCI (0.13% vs. 0.30%; RR 0.44, HR 0.47), Alzheimer's disease (0.05% vs. 0.24%; RR 0.23, HR 0.24), and Parkinson's disease (0.07% vs. 0.14%; RR 0.47; all p< 0.001). Encephalopathy (1.0% vs. 2.4%; RR 0.41), falls/fractures (6.9% vs. 9.9%; RR 0.70), delirium/psychosis (0.6% vs. 1.7%; RR 0.36), inpatient admissions (16.9% vs. 29.8%; RR 0.57), and mortality (1.8% vs. 7.1%; RR 0.26; HR 0.27) were all significantly reduced with GLP-1 therapy (all p< 0.001).
Conclusions: In T2DM patients without baseline cognitive impairment, GLP-1 agonist use was associated with substantially lower risks of MCI, Alzheimer's disease, Parkinson's disease, and all-cause mortality, alongside reduced hospitalizations and fall-related events. These findings support further investigation into GLP-1 agents as potential neuroprotective therapies in T2DM.
Disciplines
Medicine and Health Sciences | Nutritional and Metabolic Diseases
Included in
GLP-1 Receptor Agonists and Neurocognitive Outcomes in Type 2 Diabetes: A Propensity-Matched Real-World Analysis of Cognitive Impairment, Neurodegeneration, and Mortality
Background: GLP-1 receptor agonists improve glycemic and cardiovascular outcomes in type 2 diabetes mellitus (T2DM), but their impact on neurocognitive and neurological outcomes remains incompletely characterized. We evaluated the association between GLP-1 agonist use and incident cognitive impairment, neurodegeneration, and healthcare utilization in T2DM patients without baseline cognitive deficits.
Methods: A retrospective cohort study was conducted using the TriNetX Global Collaborative Network. Adults (≥40 years) with T2DM and no prior cognitive impairment, Alzheimer's disease, Parkinson's disease, multiple sclerosis, or cerebral infarction were identified. Cohort 1 received a GLP-1 agonist (semaglutide, tirzepatide, liraglutide, or dulaglutide) after T2DM diagnosis; Cohort 2 received no GLP-1 therapy. Propensity score matching (1:1) yielded 1,099,766 patients per cohort. Primary outcomes included mild cognitive impairment (MCI), Alzheimer's disease, and Parkinson's disease. Secondary outcomes included encephalopathy, falls/fractures, delirium/psychosis, inpatient admissions, and all-cause mortality. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals were estimated.
Results: GLP-1 use was associated with significantly lower risks of MCI (0.13% vs. 0.30%; RR 0.44, HR 0.47), Alzheimer's disease (0.05% vs. 0.24%; RR 0.23, HR 0.24), and Parkinson's disease (0.07% vs. 0.14%; RR 0.47; all p< 0.001). Encephalopathy (1.0% vs. 2.4%; RR 0.41), falls/fractures (6.9% vs. 9.9%; RR 0.70), delirium/psychosis (0.6% vs. 1.7%; RR 0.36), inpatient admissions (16.9% vs. 29.8%; RR 0.57), and mortality (1.8% vs. 7.1%; RR 0.26; HR 0.27) were all significantly reduced with GLP-1 therapy (all p< 0.001).
Conclusions: In T2DM patients without baseline cognitive impairment, GLP-1 agonist use was associated with substantially lower risks of MCI, Alzheimer's disease, Parkinson's disease, and all-cause mortality, alongside reduced hospitalizations and fall-related events. These findings support further investigation into GLP-1 agents as potential neuroprotective therapies in T2DM.