Evidence map›Paper›PMID 40448382›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Heterogeneous treatment effects of GLP-1RAs and SGLT2is on risk of Alzheimer's disease and related dementia in patients with type 2 diabetes: Insights from a real-world target trial emulation.

Huilin Tang, William T Donahoo, Steven T DeKosky, Yao An Lee, Pareeta Kotecha, Mikael Svensson, Jiang Bian, Jingchuan Guo

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

8 authors.

Huilin TangDepartment of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA.
William T DonahooDepartment of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.
Steven T DeKosky1Florida Alzheimer's Disease Research Center (ADRC), University of Florida, Gainesville, Florida, USA.
Yao An LeeDepartment of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA.
Pareeta KotechaDepartment of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA.
Mikael SvenssonDepartment of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA.
Jiang BianDepartment of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA.
Jingchuan GuoDepartment of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA.

Funding

Computational Drug Repurposing for AD/ADRD with Integrative Analysis of Real World Data and Biomedical KnowledgeR01AG076234 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI Jiang Bian, Fei Wang · 2022 to 2026
$3.8M
Supplement of NIDDK R01 newer GLDs and Clinical OutcomesR01DK133465 · NIDDK · UNIVERSITY OF FLORIDA · PI GUO, JINGCHUAN, SHAO, HUI · 2022 to 2025
$2.8M
iSMART: intelligent Social risk Management in AD/ADRD paTientsR01AG089445 · NIA · UNIVERSITY OF FLORIDA · PI Jiang Bian, Jingchuan Guo · 2024 to 2026
$2.2M
National Institutes of Health (NIH)/National Institute on Aging (NIA) R01AG076234National Institutes of Health (NIH)/National Institute on Aging (NIA) R01AG089445NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01DK133465The Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation Predoctoral Fellowship 2023PDVH1064032
6 · The paper itself

Abstract

introductionThis study assessed the heterogeneous treatment effects (HTEs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) on the risk of Alzheimer's disease and related dementias (ADRD).

methodsThis target trial emulation study included adults (≥ 50 years) with type 2 diabetes (T2D) and newly prescribed a GLP-1RA, SGLT2i, or other second-line glucose-lowering drugs (GLDs). A doubly robust learning approach was deployed to estimate the risk difference (RD) of ADRD and identify key subgroups.

resultsBoth GLP-1RAs (RD, -1.5%) and SGLT2is (-1.7%) were associated with a reduced ADRD risk compared to other GLDs. Key subgroups were determined based on cardiovascular disease (CVD), cerebrovascular disease (CeVD), chronic kidney disease, and Hispanic ethnicity. Patients with CVD and CeVD had the greatest benefits from GLP-1RAs (-4.8%) and SGLT2is (-4.6%). No overall difference was observed between GLP-1RAs and SGLT2i. DISCUSSION: These findings suggest the importance of personalized treatment in diabetes management regarding ADRD risk. HIGHLIGHTS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were associated with a decreased risk of Alzheimer's disease and related dementias (ADRD), while the protective association varied across subgroups defined by cardiovascular disease (CVD), cerebrovascular disease (CeVD), and chronic kidney disease (CKD). Similarly, sodium-glucose cotransporter-2 inhibitors (SGLT2is) were associated with a decreased risk of ADRD, with the protective association varying among subgroups defined by CVD, CeVD, and Hispanic ethnicity. There was no difference between GLP-1RAs and SGLT2is in the risk of ADRD.

Indexed as

Alzheimer DiseaseDementiaDiabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsSodium-Glucose Transporter 2 InhibitorsAgedFemaleHumansMaleMiddle AgedRisk FactorsTreatment Effect HeterogeneityGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsSodium-Glucose Transporter 2 InhibitorsAlzheimer's disease and related dementiasGLP‐1RAsSGLT2istype 2 diabetes

Identifiers

PMID40448382
PMCPMC12125485

What Socratic holds

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LicenceCC BY-NC
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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.