Semaglutide Use Tied to Lower Dementia Risk in Patients With Type 2 Diabetes

Treatment with semaglutide in type 2 diabetes (T2D) protects against specific dementia types, according to study results published in the Journal of Alzheimer’s Disease.

Semaglutide is believed to have the ability to target multiple risk factors and proximal mechanisms of dementia, with the potential to reduce risk for dementia in high-risk patients. Researchers have found that semaglutide and other antidiabetic medications are associated with significant risk reduction in Alzheimer disease (AD); however, there is limited data on the effect of semaglutide on other AD-related dementias.

A team of researchers conducted emulation target trials to assess the effect of semaglutide on risk for AD-related dementia (ADRD), including vascular, frontotemporal (FTP), and Lewy body dementia (LBD), in patients with T2D.

The researchers compared the effects of semaglutide with those of other antidiabetic medications on newly diagnosed ADRD for the target trials. A total of 7 patient populations (all patients; older than age 65; younger than age 65, women; men; with obesity; and without obesity) with no history of AD/ADRD were enrolled, with each population undergoing all 7 target trials.

Eligible participants for all target trials had T2D and received treatment with antidiabetic medications, with a diagnosis of at least 1 other condition (obesity, hypertension, heart disease, or kidney disease) between 2017 and 2021. Treatment with semaglutide was initiated for patients at baseline (index event).

Main study outcomes were newly diagnosed ADRD, based on the International Classification of Diseases, Tenth Revision (ICD-10)criteria; vascular dementia; frontotemporal dementia; LBD; and other dementias.

Patients were followed-up 30 days after the index event until the occurrence of outcomes, death, loss to follow-up, or 3 years after the index event, whichever occurred first.

A total of 1,710,995 patients with T2D were included in the analysis, 64,267 of whom were prescribed semaglutide and 1,646,728 other antidiabetic medications.

The researchers noted that semaglutide vs other antidiabetic medications were associated with significantly reduced risk for ADRD incidence in T2D during the 3-year follow-up (hazard ratio [HR], 0.54; 95% CI, 0.72-0.89 vs insulin; HR, 0.80; 0.72-0.89 vs glucagon-like peptide-1 agonists [GLP-1RAs]). In addition, semaglutide demonstrated sustained benefits in slowing the development of ADRD.

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Subgroup analyses were consistent with results of the primary analysis showing reductions in ADRD risk. The 3-year risk of developing ADRD with semaglutide was observed in younger and older patients (0.27% to 0.57% and 2.32% to 3.88%, respectively), with the association being stronger in the younger age group.

Similarly, significant reductions were observed among both men and women, with the association being stronger among women. Among patients with and without obesity, those with obesity had more significant risk reduction in ADRD with semaglutide.

In specific dementia types, semaglutide was associated with lower risk for vascular dementia vs with insulin (HR, 0.48; 0.39-0.59), metformin (HR, 0.55; 0.45-0.68), and GLP-1RAs (0.67; 0.54-0.84). Semaglutide was also associated with lower risks for other dementias but not FTP or LBD.

Study limitations included its retrospective observational design, which may have resulted in overdiagnosis or misdiagnosis of ADRD; lack of characterizing underlying disease mechanisms in the cohort; and the limited follow-up period.

However, overall, “These findings provide evidence supporting protective effects of semaglutide on dementias in patients with T2D,” the researchers concluded.