Evidence mapPaperPMID 41420258Full record

ArticleAlzheimer's research & therapy2025

Comparative dementia risk with GLP1 receptor agonists, SGLT2 inhibitors, or DPP4 inhibitors: a population-based cohort study.

Che-Yuan Wu, Wajd Alkabbani, Baiju R Shah, Moira K Kapral, Jodi D Edwards, Colleen J Maxwell, Walter Swardfager

Abstract readComparative Study
In one paragraph

Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Neurovascular Actions of Dipeptidyl Peptidase-4 Inhibitors and Their Implications for Cognitive Dysfunction in Type 2 Diabetes Mellitus.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Che-Yuan WuDepartment of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
Wajd AlkabbaniSchool of Pharmacy, University of Waterloo, Kitchener, ON, Canada.
Baiju R ShahDivision of Endocrinology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Moira K KapralICES, Toronto, ON, Canada.
Jodi D EdwardsSchool of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
Colleen J MaxwellSchool of Pharmacy, University of Waterloo, Kitchener, ON, Canada.
Walter SwardfagerDepartment of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. w.swardfager@utoronto.ca.

Funding

Alzheimer's Drug Discovery Foundation GC-202209-2024050Canada Excellence Research Chairs, Government of Canada CRC-2024-00213CIHR 202111FBD-47623-75801Ministry of Colleges and Universities ER21-16-146
6 · The paper itself

Abstract

backgroundWe aim to investigate comparative dementia risk associated with glucagon-like peptide-1 receptor agonists (GLP1-RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP4i) in adults aged ≥ 60 years with type 2 diabetes.

methodsThis target trial emulation cohort study used primary care electronic health records from the UK Clinical Practice Research Datalink. Initiators of GLP1-RAs, SGLT2i, or DPP4i aged ≥ 60 years with type 2 diabetes and without cognitive impairment were compared pairwise in three separate analyses. After propensity scores overlap weighting, 13,965 pairs of GLP1-RA versus DPP4i initiators (cohort entry: 2006–2022; mean age: 66.9 years), 25,533 pairs of SGLT2i versus DPP4i initiators (cohort entry: 2013–2022; mean age: 69.0 years), and 14,214 pairs of GLP1-RA versus SGLT2i initiators (cohort entry: 2013–2022; mean age: 67.9 years) were analyzed. The primary outcome was incident all-cause dementia. The primary analysis was an intention-to-treat analysis. A secondary as-treated analysis for continuous use was performed.

resultsIn the intention-to-treat analysis, dementia risk was not different between GLP1-RA and DPP4i initiators (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.87–1.04; rates: 6.29 versus 6.64 per 1000 person-years; mean follow-up: 6.54 years); however, continuous GLP1-RA versus DPP4i use was associated with a 21% lower risk (HR 0.79, 95% CI 0.64–0.97; rates: 3.64 versus 4.82; mean follow-up: 2.71 years). SGLT2i versus DPP4i initiation was associated with a 14% lower dementia risk in the intention-to-treat analysis (HR 0.86, 95% CI 0.79–0.94; rates: 4.83 versus 5.60; mean follow-up: 4.91 years), and the as-treated analysis showed greater risk reduction (HR 0.70, 95% CI 0.60–0.82; rates: 3.82 versus 5.46; mean follow-up: 2.43 years). Dementia risk was comparable between GLP1-RA versus SGLT2i in both intention-to-treat (HR 0.98, 95% CI 0.87–1.11; rates: 4.85 versus 4.95; mean follow-up: 5.09 years) and as-treated (HR 1.07, 95% CI 0.85–1.36; rates: 3.71 versus 3.56; mean follow-up: 2.40 years) analyses.

conclusionsIn people with type 2 diabetes aged ≥ 60 years, SGLT2i are associated with reduced dementia risk, but dementia risk reduction associated with the GLP1-RAs studied is less certain.

Indexed as

DementiaDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsSodium-Glucose Transporter 2 InhibitorsAgedCohort StudiesFemaleHumansMaleMiddle AgedUnited KingdomDipeptidyl-Peptidase IV InhibitorsGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsSodium-Glucose Transporter 2 Inhibitors1 (GLP1) receptor agonist, Dipeptidyl peptidase2 (SGLT2) inhibitor, Glucagon4 (DPP4) inhibitors, Diabetes, DementiaGlucose cotransporterLike peptideSodium

Identifiers

PMID41420258
PMCPMC12751920

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.