Impact of GLP-1 Receptor Agonists on Cognitive Performance in Adults at Risk of Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
9 affiliations
- 1Department of Life Sciences, Health, and Health Professions, Link Campus University, Via del Casale Pio V, 00165 Rome, Italy
- 2Department of Anaesthesia, Intensive Care and Pain Management, Campus Bio Medico University and Teaching Hospital, 00128 Rome, Italy
- 3Faculty of Medicine, Saint Camillus International University of Health Sciences, 00131 Rome, Italy
- 4Clinic of Laboratory and Precision Medicine, IRCCS INRCA, 60121 Ancona, Italy
- 5Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60100 Ancona, Italy
- 6Department of Medical and Translational Medicine, University of Naples “Federico II”, 80131 Naples, Italy
- 7Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
- 8Research Unit of Geriatrics, Università Campus Bio-Medico di Rome, 00128 Rome, Italy
- 9Operative Research Unit of Internal Medicine, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
Abstract
Background/Objectives: Type 2 diabetes, a widely recognized risk factor of Alzheimer’s disease (AD), is mainly due to the role played by insulin resistance on neuronal degeneration. Mild Cognitive Impairment (MCI) also significantly increases the risk of developing AD by approximately 40%. Epidemiological studies have demonstrated correlations between glucagon-like peptide-1 agonists (GLP-1RAs) on reducing the risk of AD. We synthesize current data from randomized controlled trials (RCTs) to summarize the effects of GLP-1RA treatment in adults with Type 2 diabetes or with MCI on cognitive performance. Methods: We searched databases from inception to 1 January 2026 investigating effects of GLP-1RA(s) on cognition. PubMed, Web of Science and Scopus databases were explored following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We selected only RCTs in adults investigating GLP-1RA(s) on cognitive performance. Results: Overall mean age was 64.5 yrs with an average follow-up period of 28.4 months. A total of 13,711 participants from five RCTs were included. Following a source-data audit, four randomized controlled trials contributed analytically compatible data to at least one cognitive domain. Cognitive domains were analyzed separately using Hedges’ g. Random-effects models used restricted maximum likelihood (REML) estimation with Knapp–Hartung inference when at least two compatible studies contributed. For global cognition, three studies yielded g = 0.014 (95% CI: −0.061 to 0.088; p = 0.515; I2 = 0%). For attention, two studies yielded g = 0.072 (95% CI: −2.164 to 2.308; p = 0.753; I2 = 31.1%). For delayed memory, executive function, and verbal function, only one compatible study was available per domain; these were therefore reported as single-study estimates rather than pooled effects. A sensitivity analysis excluding the dominant Cukierman trial yielded an imprecise and non-significant effect estimate for global cognition (g = −0.205, 95% CI: −2.678 to 2.269) indicating that the robustness of the pooled result could not be established. Conclusions: Current randomized evidence is insufficient to establish a consistent beneficial effect of GLP-1RA(s) on cognitive function in adults at risk of AD. The available findings should be considered exploratory and hypothesis-generating because few analytically compatible trials were available within each cognitive domain.
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BibTeX
@article{abbatecola2026impact,
title = {{Impact of GLP-1 Receptor Agonists on Cognitive Performance in Adults at Risk of Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials}},
author = {Angela M. Abbatecola and Giuseppe Migliara and Fausto D’Agostino and Nicola Veronese and Angelica Giuliani and Salvatore Caponnetto and Graziamaria Corbi and Elisabetta Signoriello and Raffaele Antonelli Incalzi and Giuseppe Paolisso},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18203312},
url = {https://www.mdpi.com/2072-6643/18/20/3312},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Impact of GLP-1 Receptor Agonists on Cognitive Performance in Adults at Risk of Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
AU - Angela M. Abbatecola
AU - Giuseppe Migliara
AU - Fausto D’Agostino
AU - Nicola Veronese
AU - Angelica Giuliani
AU - Salvatore Caponnetto
AU - Graziamaria Corbi
AU - Elisabetta Signoriello
AU - Raffaele Antonelli Incalzi
AU - Giuseppe Paolisso
PY - 2026
DA - 2026/10/09
JO - Nutrients
DO - 10.3390/nu18203312
UR - https://www.mdpi.com/2072-6643/18/20/3312
AB - Background/Objectives: Type 2 diabetes, a widely recognized risk factor of Alzheimer’s disease (AD), is mainly due to the role played by insulin resistance on neuronal degeneration. Mild Cognitive Impairment (MCI) also significantly increases the risk of developing AD by approximately 40%. Epidemiological studies have demonstrated correlations between glucagon-like peptide-1 agonists (GLP-1RAs) on reducing the risk of AD. We synthesize current data from randomized controlled trials (RCTs) to summarize the effects of GLP-1RA treatment in adults with Type 2 diabetes or with MCI on cognitive performance. Methods: We searched databases from inception to 1 January 2026 investigating effects of GLP-1RA(s) on cognition. PubMed, Web of Science and Scopus databases were explored following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We selected only RCTs in adults investigating GLP-1RA(s) on cognitive performance. Results: Overall mean age was 64.5 yrs with an average follow-up period of 28.4 months. A total of 13,711 participants from five RCTs were included. Following a source-data audit, four randomized controlled trials contributed analytically compatible data to at least one cognitive domain. Cognitive domains were analyzed separately using Hedges’ g. Random-effects models used restricted maximum likelihood (REML) estimation with Knapp–Hartung inference when at least two compatible studies contributed. For global cognition, three studies yielded g = 0.014 (95% CI: −0.061 to 0.088; p = 0.515; I2 = 0%). For attention, two studies yielded g = 0.072 (95% CI: −2.164 to 2.308; p = 0.753; I2 = 31.1%). For delayed memory, executive function, and verbal function, only one compatible study was available per domain; these were therefore reported as single-study estimates rather than pooled effects. A sensitivity analysis excluding the dominant Cukierman trial yielded an imprecise and non-significant effect estimate for global cognition (g = −0.205, 95% CI: −2.678 to 2.269) indicating that the robustness of the pooled result could not be established. Conclusions: Current randomized evidence is insufficient to establish a consistent beneficial effect of GLP-1RA(s) on cognitive function in adults at risk of AD. The available findings should be considered exploratory and hypothesis-generating because few analytically compatible trials were available within each cognitive domain.
SN - 2072-6643
ER -