Exploring GLP-1 drugs for Alzheimer’s prevention

Funded by a two-year, nearly $350,000 grant from the National Institutes of Health’s National Institute on Aging, the University of Cincinnati’s Shawn Xiong, PhD, is analyzing real-world patient data to learn more about how GLP-1 drugs affect people with mild cognitive impairment, a common precursor to Alzheimer’s disease.

To accomplish the research on a larger scale, Xiong is using a method called target trial emulation. The process resembles a randomized clinical trial, but instead of recruiting new patients, it will use a large global database called TriNetX that contains the de-identified health records of more than 100 million patients.

“We design the study with the exact same strict rules as a traditional trial, like who gets included, how they are matched, and how we measure success, but we apply these rules to historical medical records,” Xiong said. “This allows us to get high-quality, reliable answers much faster and cheaper. Plus, because the data comes from real-world hospitals and clinics, the results closely reflect how the drugs actually perform in everyday life, not just in a perfectly controlled lab setting.”

Using this database, Xiong and his colleagues will examine three main questions:

• Effectiveness: Do patients with mild cognitive impairment who take GLP-1s have a delayed onset of Alzheimer’s compared to those with no treatment or those taking the newly available biological drugs?
• Safety: What are the medication’s side effects in this population of older adults, and do the benefits outweigh the risks?
• Cost-effectiveness: Does it make financial sense to use GLP-1s to delay Alzheimer’s compared to current standards of care?

The most exciting aspect of the project, Xiong said, is the potential to democratize Alzheimer’s prevention if the study finds GLP-1s are safe, effective and cost-effective.

“We could rapidly transform how we treat mild cognitive impairment,” he said. “It would provide doctors and patients with an accessible tool to fight back against Alzheimer’s, drastically improving the quality of life for aging populations without bankrupting the health care system.”

Xiong received funding in his very first submission for an NIH grant, and he credited support from his mentor Jeff Guo, other colleagues in the division and college, the College of Medicine’s Center for Health Informatics, and UC Health teams that helped make his application successful.

“Because UC Health is a member of the global TriNetX network, we have the incredible privilege of accessing this massive real-world dataset that makes this entire study possible,” he said. “Tackling a public health crisis as complex as Alzheimer's truly takes a village. I feel very fortunate to be doing this work surrounded by such a supportive academic community and having access to these cutting-edge institutional resources.”

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