Semaglutide was associated with a 40% to 70% reduced risk of first-time diagnosis in patients with type 2 diabetes mellitus compared to other antidiabetic medications.
Semaglutide showed a of 0.33 for first-time Alzheimer's diagnosis compared to insulin.
When compared to other GLP-1 receptor agonists, semaglutide had a hazard ratio of 0.59.
The reduced risk associated with semaglutide was consistent across different obesity statuses, genders, and age groups.
Patients taking semaglutide had significantly lower prescriptions for Alzheimer's-related medications.
Simplified
INTRODUCTION: Emerging preclinical evidence suggests that semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration and neuroinflammation. However, real-world evidence for its ability to protect against (AD) is lacking.
METHODS: We conducted emulation target trials based on a nationwide database of electronic health records (EHRs) of 116 million US patients. Seven target trials were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide with seven other antidiabetic medications. First-ever diagnosis of AD occurred within a 3-year follow-up period and was examined using Cox proportional hazards and Kaplan-Meier survival analyses.
RESULTS: Semaglutide was associated with significantly reduced risk for first-time AD diagnosis, most strongly compared with insulin ( [HR], 0.33 [95% CI: 0.21 to 0.51]) and most weakly compared with other GLP-1RAs (HR, 0.59 [95% CI: 0.37 to 0.95]). Similar results were seen across obesity status, gender, and age groups.
DISCUSSION: These findings support further studies to assess semaglutide's potential in preventing AD.
HIGHLIGHTS: Semaglutide was associated with 40% to 70% reduced risks of first-time AD diagnosis in T2DM patients compared to other antidiabetic medications, including other GLP-1RAs. Semaglutide was associated with significantly lower AD-related medication prescriptions. Similar reductions were seen across obesity status, gender, and age groups. Our findings provide real-world evidence supporting the potential clinical benefits of semaglutide in mitigating AD initiation and development in patients with T2DM. These findings support further clinical trials to assess semaglutide's potential in delaying or preventing AD.
Key numbers
0.33
for Diagnosis ( vs. insulin)
Compared to insulin in patients over 3 years.
0.59
for Diagnosis ( vs. other )
Compared to other in patients.
1,094,761
Patient Cohort Size
Total new users of antidiabetic medications in the study.
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