by Judy George, Deputy Managing Editor, MedPage Today

By extending survival, GLP-1 agents may expand the dementia risk period for diabetes patients

Adults whose type 2 diabetes was treated with GLP-1 receptor agonists were more than likely to develop cognitive impairment over 10 years than their counterparts not treated with GLP-1 agents, a propensity-matched retrospective study of nearly 65,000 patients suggested.

Durable cognitive impairment — defined as vascular dementia, Alzheimer’s disease, or mild cognitive impairment — occurred twice as frequently in diabetes patients who used GLP-1 drugs (2.6% vs 1.3%, HR 2.74, P<0.0001), but mortality risk was lower with the drugs (3.9% vs 8.2%, HR 0.68, P<0.0001), according to Isaac Thorman, ScM, an epidemiology researcher at the Johns Hopkins University School of Medicine and a third-year medical student at New York Medical College in Valhalla, and colleagues.

On a compound outcome that assessed both cognitive impairment and mortality, there was no significant difference between GLP-1 receptor agonist users and non-users (6.1% vs 9.1%, HR 0.98, P=0.39), Thorman reported at a late-breaking science session at the American Academy of Neurology annual meeting in Chicago.

Overall, GLP-1 analogs were associated with an increased risk of cognitive impairment, secondary to a larger, protective effect against mortality, Thorman noted.

“We interpret this to mean that GLP-1 analog recipients lived significantly longer than non-recipients, and that they lived long enough for them to develop cognitive impairment,” he said.

The findings come on the heels of two phase III trials showing that Alzheimer’s patients treated with the GLP-1 agent semaglutide (Rybelsus) had no significant improvement in cognitive or functional decline over 2 years compared with placebo, Thorman noted.

“The apparent survival paradox demonstrated here, plus our unprecedented sample size and long-term follow-up, may explain the non-significance found in the randomized controlled trials,” he said.

Read more: New Kink in the Link Between GLP-1 Drugs and Cognition | MedPage Today

Source: MEDPAGETODAY