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. 2025 Sep;12(8):100199.
doi: 10.1016/j.tjpad.2025.100199. Epub 2025 May 8.

New-generation antidiabetic medications and dementia risk in older adults with type 2 diabetes: A retrospective cohort study

Avi Cohen  1 , Stephen Z Levine  2 , Gabriel Vainstein  3 , Michal Schnaider Beeri  4 , Galit Weinstein  2
Affiliations

New-generation antidiabetic medications and dementia risk in older adults with type 2 diabetes: A retrospective cohort study

Avi Cohen et al. J Prev Alzheimers Dis. 2025 Sep.

Abstract

Background: New-generation antidiabetic medications may have therapeutic potential for dementia, beyond their glycemic effects. However, information from observational studies exploring the association between new-generation antidiabetic use and dementia risk is limited.

Objectives: To examine the association between new-generation antidiabetic medication use and dementia risk.

Design: Retrospective cohort study using electronic health records of a large non-profit health maintenance organization.

Participants: 84,798 dementia-free individuals aged ≥65y with type 2 diabetes.

Measurements: Antidiabetic medication exposure was based on purchased prescriptions and was used as a time-varying variable. Exposure periods were defined as periods in which either dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or glucagon-like peptide-1 analogs (GLP-1a) or their combinations were used, otherwise unexposed. Dementia classification was based on the International Classification of Diseases, Ninth Revision codes or antidementia medication prescriptions. Cox regression models were fitted to quantify the association between antidiabetic medication use and incident dementia. Models were adjusted for 13 potential sources of confounding using inverse-probability weighting.

Results: Among 84,798 individuals with a mean diabetes onset age of 66.4 ± 7.5 years, the median follow-up for dementia risk was 8.7 years (Q1-Q3: 5.4-12.8). Dementia was diagnosed in 11,642 (13.7%) individuals. New-generation medication use was associated with reduced dementia risk (HR = 0.69; 95% CI, 0.66-0.73) and by drug classes (DPP-4i, HR 0.67 [95% CI 0.63-0.71]; SGLT-2i, 0.63 [95% CI 0.56-0.70], GLP-1a, 0.61 [95% CI 0.54-0.69].

Conclusions: The results of this large-scale study suggest that new-generation antidiabetic medication use may be associated with lower dementia risk in older adults with T2D.

Keywords: Dementia; Diabetes; Dipeptidyl peptidase‐4 inhibitors (DPP-4i); Glucagon-like peptide-1 analogues (GLP-1a); Sodium-glucose cotransporter-2 inhibitors (SGLT-2i).

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Avi Cohen reports financial support was provided by Alzheimer’s Association. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig 1
Fig. 1
Study sample flowchart.
Fig 2
Fig. 2
Adjusted and weighted hazard ratio for dementia in the different models.
See this image and copyright information in PMC

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