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Meta-Analysis
. 2023 Jul;71(7):2096-2106.
doi: 10.1111/jgs.18306. Epub 2023 Feb 23.

Newer glucose-lowering drugs and risk of dementia: A systematic review and meta-analysis of observational studies

Huilin Tang  1 , Hui Shao  1   2 , C Elizabeth Shaaban  3 , Keming Yang  4 , Joshua Brown  1   2 , Stephen Anton  5   6 , Yonghui Wu  7 , Adam Bress  8 , William T Donahoo  9 , Steven T DeKosky  10   11 , Jiang Bian  7 , Jingchuan Guo  1   2
Affiliations
Meta-Analysis

Newer glucose-lowering drugs and risk of dementia: A systematic review and meta-analysis of observational studies

Huilin Tang et al. J Am Geriatr Soc. 2023 Jul.

Abstract

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.

Keywords: DPP-4 inhibitors; GLP-1RAs; SGLT2 inhibitors; dementia; type 2 diabetes.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
The flowchart of study selection
Figure 2.
Figure 2.
Meta-analysis of the association between SGLT2 inhibitor users and risk of all-cause dementia as compared to non-SGLT2 inhibitor users. The size of the square represents the weight of each study contributing to the overall meta-analysis.
Figure 3.
Figure 3.
Meta-analysis of the association between GLP-1RA users and risk of all-cause dementia as compared to non-GLP-1RA users. The size of the square represents the weight of each study contributing to the overall meta-analysis.
Figure 4.
Figure 4.
Meta-analysis of the association between DPP-4 inhibitors and risk of all-cause dementia, Alzheimer’s disease, and vascular dementia as compared to non-DPP-4 inhibitor users. The size of the square represents the weight of each study contributing to the overall meta-analysis.
See this image and copyright information in PMC

Comment in

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