Researchers at the Case Western Reserve School of Medicine have found that, when compared to seven other anti-diabetic drugs, semaglutide, a popular diabetes and weight-loss drug, may lower the risk of Alzheimer’s disease in people with type 2 diabetes (T2D).
Alzheimer’s disease is a brain disorder that slowly destroys memory and thinking skills. According to the Alzheimer’s Association, nearly 7 million Americans 65 and older are living with the disease, and there are more deaths from Alzheimer’s than breast and prostate cancer combined.
This retrospective observational study, published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, suggests T2D patients taking semaglutide had a significantly lower risk of developing Alzheimer’s disease. These results were consistent across different subgroups, including obesity status, gender, and age.
Semaglutide, a glucagon-like peptide receptor (GLP-1R) molecule that decreases hunger and helps regulate blood sugar in T2D, is also the active component in the diabetes and weight-loss drugs Wegovy and Ozempic.
“Obesity is now recognized as a major modifiable risk factor of AD and related dementia in the United States,” noted the study authors. “These findings suggest that semaglutide may have beneficial effects on delaying the onset of AD through mechanisms beyond weight loss.”
Investigating the popular new drug
The research team — led by biomedical informatics professor Rong Xu — analyzed three years of electronic records of nearly 1 million U.S. patients with T2D. The researchers used a statistical approach that mimics a randomized clinical trial.
They found patients prescribed semaglutide had a significantly lower risk for Alzheimer’s disease, compared to those who had taken any of seven other anti-diabetic medications, including other types of GLP-1R-targeting medications, insulin, metformin, DPP-4i, SGLT2i, SU, and TZD.
About 120,000 Americans die from Alzheimer’s disease each year, with the disease listed as the seventh-leading cause of death nationally, according to the CDC.
“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,” said Xu, who also directs the medical school’s Center for AI in Drug Discovery and is a member of the Cancer Genomics Epigenomics Program at the Case Cancer Comprehensive Center.
Although their findings potentially support the idea that semaglutide could prevent Alzheimer’s disease, the study’s limitations restrict the researchers from making firm causal conclusions, she said.
“Our results indicate that further research into semaglutide’s use will need to be further investigated through randomized clinical trials so alternative drugs can be tested as potential treatment for this debilitating illness,” Xu said.
Conclusion
“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. Additional preclinical and clinical studies are needed to shed light on the mechanisms of the potential benefits of semaglutide in preventing or delaying the onset of AD and establish causal effects through randomized trials.”
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This article was written by Patty Zamora at Case Western Reserve University
