Semaglutide linked to reduced risk for Alzheimer’s in patients with diabetes
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Key takeaways:
- Semaglutide was associated with a 40% to 70% lower risk for AD diagnosis within 3 years vs. other diabetes drugs.
- The study provides real-world evidence that supports previous preclinical data.
In patients with type 2 diabetes, semaglutide was associated with a significantly lower risk for an Alzheimer’s disease diagnosis within 3 years compared with other diabetes medications, according to a study published in Alzheimer’s & Dementia.
“Semaglutide, a glucagon-like peptide-1 receptor agonist, was approved by the FDA for type 2 diabetes mellitus in 2017 and for weight loss in 2021. Both are significant modifiable risk factors for AD,” Rong Xu, PhD, professor of biomedical informatics and director of the Center for AI in Drug Discovery at Case Western Reserve School of Medicine, and colleagues wrote. “Furthermore, semaglutide has demonstrated benefits in managing various other health conditions such as cardiovascular factors, alcohol use, smoking and depression, many of which are also linked to AD risk.”
Building on preclinical evidence that suggests semaglutide (Novo Nordisk) protects against neurodegeneration and neuroinflammation consistent with AD, Xu and colleagues assessed its potential for delaying or preventing AD in a real-world setting.
The researchers culled data from electronic health records of 116 million individuals in the United States. They then emulated seven target trials of more than 1 million eligible patients with type 2 diabetes mellitus aged 60 years or older, including those with and without obesity, to compare first-time AD diagnoses among those who received semaglutide vs. other diabetes medications over 3 years of follow up.
According to the results, individuals prescribed semaglutide had a 40% to 70% lower risk for a first-time AD diagnosis within that 3-year window compared with the other medications.
Data showed that the association was strongest between semaglutide and insulin (HR = 0.33; 95% CI, 0.21-0.51), but weakest when compared with alternate GLP-1 receptor agonists (HR = 0.59; 95% CI, 0.37-0.95).
The researchers also found that, when controlling for age, the overall risk for first-time AD diagnosis was twice as high in those aged 60 years and older (0.33 vs. 0.16) compared with the general population within the EHRs.
Additionally, the results demonstrated a similar drop in first-time AD diagnoses for those administered semaglutide in the general population, and it was also tied to fewer prescriptions for AD-related medications.
“This new study provides real-world evidence for its impact on Alzheimer’s disease, even though preclinical research has suggested that semaglutide may protect against neurodegeneration and neuroinflammation,” Xu said in a release related to the study.
Reference:
Popular diabetes and weight-loss drug may reduce risk of Alzheimer’s disease. https://www.eurekalert.org/news-releases/1061949?. Published Oct. 24, 2024. Accessed Oct. 25, 2024.
Perspective
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Diabetes is a known risk factor for AD, and managing diabetes with drugs like semaglutide could benefit brain health simply by managing diabetes. However, we still need large clinical trials in representative populations to determine if semaglutide specifically lowers the risk of AD, so it is too early to recommend it for prevention.
Some research suggests that semaglutide, which belongs to a class of drugs called GLP-1 receptor agonists, may help reduce inflammation and positively impact brain energy use. However, more research is needed to fully understand how these processes might contribute to preventing cognitive decline or AD.
The Alzheimer’s Association has a list of 10 Healthy Habits for Your Brain, which includes managing diabetes. These are ways to protect your brain and reduce the risk of cognitive decline, and possibly also dementia. They include: challenge your mind, protect your head and control your blood pressure. It’s never too early or too late to start.
The Alzheimer’s Association is the largest nonprofit funder of AD and dementia research, currently funding $430 million across 1,110 projects in 56 countries. This includes work focused on the basic mechanisms of brain metabolism all the way to clinical trials.
The association’s Part the Cloud initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that may address known and potential new aspects of the disease. Related to this work, Paul Edison, MBBS, FRCP, PhD, was funded by Part The Cloud for a clinical trial of oral semaglutide, branded Rybelsus (Novo Nordisk). We look forward to hearing the results from this study and other trials looking into this class of medication.
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