Dementia progression with GLP-1 receptor agonists in people with mild cognitive impairment and type 2 diabetes: target-trial emulation study.

Authors

Meir Schechter, Dvora R Sehtman-Shachar, Alisa Fishkin, Ofri Mosenzon, Tali Cukierman-Yaffe, Ronit Sharon, Gil Leibowitz, David Arkadir, Genya Aharon-Hananel

Published in

Alzheimer's & dementia (New York, N. Y.). Volume 12. Issue 3. Pages e70315. Epub Sep 20, 2026.

Abstract

In people with type 2 diabetes (T2D) without dementia, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved cardiovascular, kidney, and mortality outcomes, with multiple real-world studies suggesting reduced risk of dementia onset. However, the EVOKE/EVOKE+ randomized-controlled trials (RCTs) found that oral semaglutide did not slow cognitive decline in individuals with early Alzheimer's disease (AD), most (86%) without T2D. It is unclear whether GLP-1 RA therapy influences progression to dementia in people with both T2D and mild cognitive impairment (MCI).
In a target-trial emulation hypothesis-generating study using TriNetX global collaborative network data, we compared incident dementia (including AD) in adults with MCI and T2D without dementia, who were new users of GLP-1 RAs versus dipeptidyl peptidase-4 inhibitors (DPP4i).
We included 1320 propensity-score-matched (1:1) individuals who initiated GLP-1 RAs or DPP4i in the period 2010 to 2021 (702 women; mean age 67.2 years). Over up to 5 years of follow-up, incident dementia occurred in 101 and 132 participants initiating GLP-1 RAs and DPP4i, respectively (Cox proportional hazard ratio 0.74 [95% confidence interval [CI]: 0.57 to 0.95]). At a mean follow-up of 3.9 years, the respective Kaplan-Meier-derived cumulative incidences were 15.5% and 20.4% (absolute difference -4.9% [95% CI -9.4 to -0.4], number needed to treat of 21 [11 to 234] individuals to prevent one event). Various sensitivity analyses supported the primary analysis: comparing GLP-1 RAs with basal insulin, using alternative outcome definitions, repeating the analyses across baseline subgroups, and using a negative control outcome.
In this hypothesis-generating study, initiation of GLP-1 RAs versus DPP4i in people with T2D and MCI without dementia was associated with a lower risk of incident dementia.

PMID:
42769274
Bibliographic data and abstract were imported from PubMed on 22 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.