Journal of the American Geriatrics SocietyFeb 23, 2023

Newer diabetes drugs and their link to dementia risk

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 28, 2026

Abstract

Ten studies involving 819,511 individuals with type 2 diabetes were analyzed for the association between newer glucose-lowering drugs and dementia risk.

Users of SGLT2 inhibitors showed a lower risk of all-cause dementia compared to non-users (relative risk, 0.62; 95% confidence interval, 0.39-0.97).
GLP-1 receptor agonist users were associated with a significant reduction in the risk of all-cause dementia (relative risk, 0.72; 95% confidence interval, 0.54-0.97).
DPP-4 inhibitor users were significantly associated with a decreased risk of all-cause dementia (relative risk, 0.84; 95% confidence interval, 0.74-0.94) and vascular dementia (relative risk, 0.59; 95% confidence interval, 0.47-0.75).
No significant association was found between DPP-4 inhibitors and Alzheimer's disease risk (relative risk, 0.82; 95% confidence interval, 0.63-1.08).
The results indicate a potential protective effect of newer GLDs against dementia in adults with type 2 diabetes, although caution is advised due to the observational nature of the studies.

Simplified

BACKGROUND: Preclinical studies have suggested potential beneficial effects of newer glucose-lowering drugs (GLDs) including dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium glucose co-transporter-2 (SGLT2) inhibitors, in protecting humans against cognitive decline and dementia. However, population studies aiming to demonstrate such cognitive benefits from newer GLDs have produced mixed findings. This meta-analysis aimed to evaluate the association between newer GLDs and risk of dementia in adults with type 2 diabetes (T2D).

METHODS: Electronic databases were searched up to March 11, 2022 to include observational studies that examined the association between DPP-4 inhibitors, GLP-1RAs, and SGLT2 inhibitors and risk of dementia (including all-cause dementia, Alzheimer's disease [AD], and vascular dementia [VD]) in people with T2D. We conducted a random-effects meta-analysis to calculate the relative risk (RR) with 95% confidence interval (CI) for each class of newer GLD.

RESULTS: Ten studies (from nine articles) involving 819,511 individuals with T2D were included. Three studies found that SGLT2 inhibitor users had a lower risk of all-cause dementia than non-SGLT2 inhibitor users (RR, 0.62; 95% CI, 0.39-0.97). Five studies found that users versus nonusers of GLP-1RAs were associated with a significant reduction in the risk of all-cause dementia (RR, 0.72; 95% CI, 0.54-0.97). However, a meta-analysis for AD and VD was unavailable for SGLT2 inhibitors and GLP-1RAs because only one study was included for each drug. In seven studies, users vs. nonusers of DPP-4 inhibitors were significantly associated with a decreased risk of all-cause dementia (RR, 0.84; 95% CI, 0.74-0.94) and VD (RR, 0.59; 95% CI, 0.47-0.75) but not AD (RR, 0.82; 95% CI, 0.63-1.08).

CONCLUSION: Newer GLDs were associated with a decreased risk of all-cause dementia in people with T2D. Because of the observational nature and significant heterogeneity between studies, the results should be interpreted with caution. Further research is warranted to confirm our findings.

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CONFLICT OF INTEREST. The authors declare that there is no conflict of interest.

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Newer diabetes drugs and their link to dementia risk

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