Comparative risks of dementia and Parkinson's disease with GLP-1 RAs versus other oral glucose-lowering medications in obese patients with type 2 diabetes: a large real-world cohort study.

Authors

Wiessam Abu Ahmad, Yael Wolff Sagy, Ronen Arbel, Erez Battat, Dror Dicker, Gil Lavie, Orna Reges

Published in

European journal of internal medicine. Pages 107164. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

This study evaluates dementia and Parkinson's disease (PD) risk among patients with type 2 diabetes (T2D) and obesity initiating GLP-1 receptor agonists (GLP-1 RAs) compared with other oral glucose-lowering medications, addressing the unclear comparative neurocognitive effects despite GLP-1 RAs' neuroprotective potential in preclinical studies.
This historical prospective cohort study used electronic health records from Clalit Health Services. Adults with T2D and obesity (body mass index [BMI] ≥30 kg/m²) initiating non-insulin glucose-lowering medications between 2008-2021 were included. After exclusions and 1:1 nearest-neighbor matching, the final cohort comprised 46,962 patients. Associations were assessed using Cox proportional hazards models.
Among 46,962 matched participants (mean age, 62.8 years; 52.6% women), median follow-up period was 7 years. Dementia occurred in 1125 GLP-1 RA users (4.8%) and 1822 non-GLP-1 users (7.8%) (adjusted hazard ratio [HR], 0.86 (0.75-0.99)). PD occurred in 231 GLP-1 RA users (1.0%) and 338 non-GLP-1 users (1.4%) (0.90 (0.67-1.22)). In the secondary analysis, GLP-1 RA use was associated with lower risks of dementia compared with sulfonylureas (0.75 (0.61-0.93)) and PD (0.56 (0.36-0.86)). No significant differences were observed compared with DPP-4 inhibitors or SGLT2 inhibitors. Subgroup analyses showed stronger protective associations for dementia among women (0.78 (0.65-0.94)) and participants aged ≥65 years (0.82 (0.69-0.97)).
The use of GLP-1 RAs was associated with a lower risk of dementia compared with other glucose-lowering therapies. These findings support the neuroprotective potential of GLP-1 RAs and highlight the importance of incorporating brain health into diabetes management strategies.

PMID:
42629262
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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