Diabetes, obesity & metabolismNov 27, 2025

Comparing SGLT2 inhibitors and GLP-1 receptor agonists for new cases of dementia

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 20, 2026

Abstract

Among 32,542 adults with type 2 diabetes, 581 using GLP-1 receptor agonists and 572 using SGLT2 inhibitors developed dementia during a median 6.3-year follow-up.

No significant differences in the risk of all-cause dementia were found between users of GLP-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors.
The hazard ratio for all-cause dementia was 1.01, indicating a similar risk for both medication groups.
Subgroup analyses supported the absence of significant differences in the incidence of vascular and Alzheimer's dementia.
SGLT2 inhibitor use was not associated with an increased risk of dementia compared to GLP-1 receptor agonists.

Simplified

OBJECTIVE: This study provides real-world evidence on the comparative effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) regarding the risk of incident dementia in adults with type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS: This cohort study utilised electronic health records from TriNetX (1 April 2013 to 31 December 2019). Adults with T2DM on metformin who initiated GLP-1 RAs or SGLT2i were analysed using Cox proportional hazards models in 1:1 propensity score-matched cohorts. The primary outcome was all-cause dementia; secondary outcomes included vascular and Alzheimer's dementia. Confounding variables were adjusted.

RESULTS: Among 16 271 participants using GLP-1 RAs and 16 271 using SGLT2i over a median 6.3-year follow-up, 581 GLP-1 RA users and 572 SGLT2i users developed dementia. No significant differences were observed in all-cause dementia (hazard ratio: 1.01, 95% confidence interval: 0.90-1.13), vascular, or Alzheimer's dementia. Subgroup analyses confirmed these findings.

CONCLUSIONS: SGLT2i use was not associated with increased risk of dementia compared with GLP-1RAs in patients with T2DM. Further research is warranted to explore the effects of (newer) incretin-based (co-)agonists on cognitive outcomes.

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Funding

Competing interests

FA, SN and GA have no competing interests. MK receives funding support from an MD‐PhD grant from the University Medical Center Groningen. Over the past 3 years, CSM reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer Ingelheim; he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Nestlé, Amgen, Corcept, Aligos, Intercept, 89 Bio, Madrigal, Novo Nordisk and Regeneron, reports travel support and fees from TMIOA, Elsevier and the Cardio Metabolic Health Conference. No consulting activity above is related to the work presented herein.

PubMed

Comparing SGLT2 inhibitors and GLP-1 receptor agonists for new cases of dementia

Abstract

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Competing interests

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Abstract

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