Semaglutide May Reduce Alzheimer’s Risk in Adults with T2D: Daily Dose

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Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

On October 25, 2024, we reported on a study published in the journal Alzheimer’s & Dementia that examined whether semaglutide is associated with a reduced risk for first-time diagnoses of Alzheimer disease (AD) in a high-risk population, stratified by gender, age groups, and obesity status.

The study

To simulate a randomized clinical trial, investigators conducted 7 emulation target trials based on a national database of electronic health records (EHR) of 116 million individuals. The researchers identified 1 094 761 adults with type 2 diabetes (T2D) without a diagnosis of AD, including 17 104 new users of semaglutide and 1 077 657 new users of 7 other antidiabetic medication classes: other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylureas, and thiazolidinediones.

The primary study outcome was an EHR-documented first-time diagnosis of AD with AD-related medication prescriptions used as secondary outcomes. All eligible participants were followed from index event until the occurrence of the outcome, death, loss to follow-up, or 3 years after the index event, whichever occurred first. The 6 populations assessed were all patients, older patients (≥60), women, men, patients with obesity, and patients without obesity.

Individuals who were eligible had T2D and medical encounters between December 2017 and May 2021, had no use of any antidiabetic medications within the past 6 months (ie, new users), and had been diagnosed with at least 1 condition included in the labeling for semaglutide (eg, obesity, hypertension, hypercholesterolemia, heart diseases, stroke, or HbA1C ≥8.5%).

The findings

Semaglutide was associated with 40% to 70% reduced risks of first-time AD diagnosis in patients with T2D compared to other antidiabetic medications, including other GLP-1RAs. Researchers reported consistent results for reduced risk across study subgroups, classified by age, gender, and obesity status.

Patients with T2D who were prescribed semaglutide had a significantly decreased risk of receiving a first-time diagnosis of AD during a 3-year follow-up compared with those prescribed other antidiabetic medications. The largest reduction in risk was seen in comparison with insulin (HR 0.33, 95% CI 0.21-0.51) and the smallest was against other GLP-RAs (HR 0.59, 95% CI 0.37-0.95).

Authors' comment

"Our findings support further clinical evaluation of semaglutide's role in mitigating AD initiation and development in patients with T2DM. Future research should explore its effects in mild cognitive impairment, other dementias, and neurodegenerative diseases, as well as investigate other GLP-1RAs like tirzepitide and combination therapies with other antidiabetic medications."

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