Semaglutide (also known as Ozempic) is a popular medication for type 2 diabetes and weight loss. The study compared semaglutide to seven other antidiabetic medications and found that it was associated with a significantly lower risk of developing Alzheimer’s.
An estimated 6.9 million Americans over the age of 65 will be living with Alzheimer’s disease (AD) by 2024, and that number could more than double by 2060, reaching 13.8 million.
AD currently has no cure and has profound social and economic impacts. However, studies indicate that about 40% of cases are related to modifiable risk factors, that is, factors that, if controlled, could help prevent or delay the disease.
One of the risk factors for Alzheimer’s is type 2 diabetes (T2D), a condition that is also associated with other health problems, such as obesity and cardiovascular disease. Semaglutide (also known as Ozempic), approved for the treatment of T2D and weight loss in the US, acts on the GLP-1 receptor, helping to control diabetes.
Recent studies suggest that, in addition to helping control diabetes, semaglutide could have neuroprotective effects. This raises the hypothesis that the drug could also reduce the risk of developing Alzheimer’s in people at high risk for the disease.
To explore this possibility, researchers at Case Western University used electronic medical record data from 1.09 million patients with T2D and no previous diagnosis of AD.
The study compared the use of semaglutide with other diabetes medications, including insulin and other GLP-1 agonists (such as liraglutide). Over a 3-year follow-up, patients who used semaglutide had a significantly lower risk of being diagnosed with Alzheimer’s compared with those who used insulin and other medications.
The study found that there was a significant difference between men and women in the effect of semaglutide on the risk of developing Alzheimer’s. In women with type 2 diabetes, semaglutide was associated with a more pronounced reduction in the risk of a first diagnosis of Alzheimer’s than in men.
Specifically, the study found a 78% reduced risk for women compared with a 52% reduction for men.
This difference suggests that semaglutide may have a stronger protective effect in women, although more studies are needed to confirm these findings and understand the mechanisms underlying this difference.
In addition, the health profiles between the populations of men and women in this study varied: women were, on average, younger, had higher rates of obesity and depression, and lower rates of cardiovascular disease, which may have influenced the results.
This discovery reinforces the importance of carrying out separate analyses for each gender, especially in research on diseases such as Alzheimer's, which is more prevalent in women.
The protective effects of semaglutide may go beyond controlling diabetes. Studies indicate that it can reduce inflammation in the brain, a factor linked to Alzheimer's, and improve glucose uptake, which is essential for neuronal function. In addition, evidence suggests that semaglutide helps reduce beta-amyloid plaque deposits, which are characteristic of Alzheimer's.
In addition to the direct benefits in the brain, semaglutide also positively impacts other health conditions that can increase the risk of Alzheimer's, such as depression and cardiovascular disease. This strengthens the hypothesis that it may contribute to the prevention of Alzheimer's by mitigating these risk factors.
The promising results of this observational study pave the way for further research, especially clinical trials, to understand whether semaglutide can delay or prevent Alzheimer's.
Such trials would be important to confirm the observed effects and better understand the mechanisms by which the drug could act to protect against AD.
For now, although the findings are encouraging, caution is needed. The observed effects are significant, but definitive confirmation will only come with more robust clinical studies and long-term monitoring, which will help to clarify whether semaglutide can be an ally in the fight against Alzheimer's.
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Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US
William Wang, QuangQiu Wang, Xin Qi, Mark Gurney, George Perry, Nora D. Volkow, Pamela B. Davis, David C. Kaelber, Rong Xu
Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
24 October 2024
Abstract:
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 Alzheimer's disease (AD) is lacking. 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. Semaglutide was associated with significantly reduced risk for first-time AD diagnosis, most strongly compared with insulin (hazard ratio [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. These findings support further studies to assess semaglutide's potential in preventing AD.
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