Semaglutide, dulaglutide help prevent cognitive decline in HF patients

Treatment with semaglutide and dulaglutide results in a significantly lower risk of adverse cognitive decline in patients with heart failure (HF), as shown by the results of a retrospective cohort study using real-world data.

“Semaglutide and dulaglutide were associated with reduced cognitive decline in heart failure, particularly vascular dementia,” said lead author Andreas Kalogeropoulus, associate professor at Stony Brook University, Stony Brook, New York, US.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide and dulaglutide, have shown neuroprotective effects in previous studies involving patients with diabetes mellitus (DM). However, their impact on cognitive function in HF patients remains unclear.

To address this gap, Kalogeropoulus and his team conducted a retrospective cohort study using real-world data from a global collaborative network. They included a total of 35,619 patients with HF, with or without DM, who were prescribed semaglutide, dulaglutide, or liraglutide between 1 January 2019 and 31 December 2022 (mean age 69.5 years, 47.6–52.0 percent male; 61.5–67.6 percent White).

Using propensity score matching to balance baseline characteristics, the authors matched participants 1:1 (separately for each drug) with non-GLP-1RA users.

The primary outcomes, assessed at 1 year, were as follows: incident Alzheimer’s disease (AD), mild cognitive impairment (MCI), any dementia, and vascular dementia based on respective ICD-10 codes (G30, G31.84, F03, and F01, respectively). Finally, hazard ratios (HRs) with 95 percent confidence intervals (CIs) were calculated using Cox proportional hazard regression.

Diabetes was most prevalent among patients prescribed dulaglutide (89.0 percent), while prevalence among liraglutide and semaglutide users was 76.9 percent and 74.8 percent, respectively. Obesity prevalence was highest among semaglutide users (71.6 percent) relative to those on dulaglutide (55.5 percent) or liraglutide (55.0 percent). [Kalogeropoulus A, et al, ESC 2025]

The use of semaglutide and dulaglutide correlated with a significantly reduced risk of developing any dementia in patients with HF, HF with reduced ejection fraction (HFrEF), and HF with preserved ejection fraction (HFpEF; p<0.001).

Vascular dementia

Furthermore, patients with HF, HFrEF, and HFpEF who are taking semaglutide benefitted from a reduced risk of MCI, while those with HFpEF also showed a lower risk of AD. On the other hand, dulaglutide use resulted in a reduced risk of MCI in patients with HF and a lower risk of vascular dementia in those with HFpEF.

Notably, treatment with semaglutide and dulaglutide conferred a stronger protective effect against vascular dementia than AD. This finding indicated a vascular mechanism of cognitive protection, according to Kalogeropoulus.

“The greater reduction in vascular dementia compared with AD, especially with semaglutide, suggests GLP-1RAs may mitigate vascular contributions to cognitive impairment through improved endothelial function and reduced inflammation,” he said.

On the other hand, treatment with liraglutide fell short of demonstrating significant cognitive protection across HF subtypes.

“These findings suggest GLP-1RAs may offer vascular neuroprotection and warrant further study in prospective trials,” said Kalogeropoulus.