Semaglutide Linked to Lower Dementia Risk in Type 2 Diabetes

Semaglutide was associated with a significantly reduced risk of Alzheimer disease-related dementia (ADRD), including vascular dementia, when compared with insulin, metformin, and older glucagon-like peptide-1 receptor agonists (GLP-1RAs), new research shows.¹ With nearly half of all dementia cases considered preventable, these findings highlight the potential of semaglutide to mitigate this risk.²

An analysis of 1.7 million patients shows semaglutide may significantly reduce Alzheimer and vascular dementia risk compared with other diabetes drugs. | Image Credit: K KStock - stock.adobe.com

The emulated trial analysis is published in the Journal of Alzheimer’s Disease.¹

“In a real-world population with T2D [type 2 diabetes] who had no prior diagnosis of AD/ADRD [Alzheimer disease/Alzheimer disease-related dementia], our study shows that semaglutide was associated with a significantly lower risk of overall ADRD incidence compared with other antidiabetic medications, including insulin, metformin, and other GLP-1RAs,” wrote the researchers of the study. “Significant reductions were observed in older and younger patients, women and men, and patients with and without obesity.”

The study utilized a target trial emulation approach based on a comprehensive, nationwide US electronic health record database comprising 1,710,995 eligible adults with type 2 diabetes (T2D). Researchers compared patients initiating semaglutide with those starting other antidiabetic medications, including insulin, metformin, and older-generation GLP-1RAs. Individuals with a prior diagnosis of ADRD were excluded.

Dementia outcomes—including AD, vascular dementia, frontotemporal dementia, and Lewy body dementia—were assessed over a 3-year follow-up period, as well as survival analyses to estimate risk differentials.

Patients on semaglutide were found to have a 46% lower risk of ADRD compared with those on insulin (HR, 0.54; 95% CI, 0.49-0.59), a 33% lower risk compared with metformin (HR, 0.67; 95% CI, 0.61-0.74), and a 20% lower risk compared with older-generation GLP-1 RAs (HR, 0.80; 95% CI, 0.72–0.89). The protective effect was particularly strong for vascular dementia, while no significant association was found for frontotemporal dementia or Lewy body dementia.

However, the researchers acknowledged several study limitations. Although a significant reduction in ADRD risk was observed among a high-risk population with T2D and substantial comorbidities, future research should assess longer-term outcomes and more diverse populations. Additionally, the study relied on International Classification of Diseases, 10th Revision codes for dementia diagnosis, which are subject to underdiagnosis and misclassification, though consistent data sources across treatment groups support the validity of relative risk comparisons. Other limitations include a lack of data on medication adherence, cognitive assessments, and genomic profiles, as well as unmeasured variation in clinical practices and healthcare utilization.

Despite these limitations, the researchers believe the findings suggest a potential neuroprotective benefit of semaglutide in patients with T2D, especially in reducing the risk of more common dementia subtypes.

“As we and others have previously shown benefit for semaglutide and other GLP-1RA medications in AD, our results support the GLP-1 receptor as a target for dementia prevention,” wrote the researchers. “Preclinical and clinical studies are necessary to understand the mechanisms and establish causal effects through randomized trials. Economic and policy analyses are needed to examine the cost-effectiveness of integrating semaglutide and other pharmacotherapy-based prevention strategies with existing behavior-based approaches, such as exercise and diet, in achieving substantial benefits for preserving cognitive function and preventing AD and related dementias.”

References

1. Wang W, Davis PB, Qi X, et al. Associations of semaglutide with Alzheimer’s disease-related dementias in patients with type 2 diabetes: A real-world target trial emulation study. Journal of Alzheimer’s Disease. 2025;0(0). doi:10.1177/13872877251351329

2. Dementia prevention, intervention, and care 2024. The Lancet. July 31, 2024. Accessed June 24, 2025. https://www.thelancet.com/commissions-do/dementia-prevention-intervention-and-care