Title

GLP-1 receptor agonists versus Sitagliptin and incident Alzheimer's disease in type 2 diabetes: A propensity score-matched TriNetX cohort study

Authors

Meet P. Kachhadia¹, Piyush Puri², Usmaan Topiwala³, Parth Pambhar⁴, Akshara Dhami⁴, Juber D. Shaikh⁵, Gurnoor Gill¹, Samarth Shah⁶, Jay Patel⁷ & Harshal A. Sanghvi^8,*

Affiliation

¹Department of Neurology, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA; ²Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, NYC Health + Hospitals/Queens, New York, NY, USA; ³Smt. NHL Municipal Medical College, Ahmedabad, Gujarat, India; ⁴Prime Healthcare, IL, USA; ⁵Department of Neurology, Henry Ford Hospital, Detroit, MI, USA; ⁶Department of Technology and Clinical Trials, Advanced Research LLC, FL, USA; ⁷Department of Biomedical Engineering, Florida Atlantic University, Boca Raton, FL, USA; ⁸Department of Information Technology and Operations Management, College of Business, Florida Atlantic University, Boca Raton, FL, USA; *Corresponding author

Email

Meet P. Kachhadia - E-mail: mkachhadia@health.fau.edu
Piyush Puri - E-mail: piyush.puri@mssm.edu
Usmaan Topiwala - E-mail: usmaantopiwala@gmail.com
Parth Pambhar - E-mail: parthpambhar@gmail.com
Akshara Dhami - E-mail: akidhami24@gmail.com
Juber D. Shaikh - E-mail: jubershaikh703@yahoo.com
Gurnoor Gill - E-mail: ggill2023@health.fau.edu
Samarth Shah - E-mail: samarthshah341@gmail.com
Jay Patel - E-mail: jay16501@gmail.com
Harshal A. Sanghvi - E-mail: hsanghvi2020@fau.edu

Article Type

Research Article

Date

Received August 1, 2026; Revised August 31, 2026; Accepted August 31, 2026, Published August 31, 2026

Abstract

Type 2 diabetes mellitus (T2DM) raises Alzheimer's disease (AD) risk and GLP-1 receptor agonists (GLP-1 RAs) show neuroprotective signals, yet head-to-head comparisons against sitagliptin are limited. Using the TriNetX US Collaborative Network, we propensity score-matched T2DM patients prescribed GLP-1 RAs versus sitagliptin (198,976 per cohort) for incident AD and a broad dementia composite. Incident AD occurred in 0.51% versus 1.80% (hazard ratio 0.452; 95% CI 0.421-0.486; P < 0.001). The dementia composite occurred in 3.03% versus 8.58% (hazard ratio 0.553; 95% CI 0.536-0.570; P < 0.001). Thus, data shows that given substantial follow-up imbalance and a non-standard multi-agent exposure definition, these associations are hypothesis-generating rather than evidence of causal neuroprotection.

Keywords

GLP-1 receptor agonists (GLP-1 RAs), Alzheimer's disease (AD), type 2 diabetes mellitus (T2DM), dementia, sitagliptin, propensity score matching, TriNetX

Citation

Kachhadia et al. Bioinformation 22(8): 4688-4692 (2026)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.