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Uncovering the Therapeutic Potential of Semaglutide in Alzheimer's Disease: Insights from Animal Models and Real-World Clinical Data

Award Number: R01AG099323
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Uncovering the Therapeutic Potential of Semaglutide in Alzheimer's Disease: Insights from Animal Models and Real-World Clinical Data - PROJECT SUMMARY Alzheimer's disease (AD) is the most common cause of dementia and a leading cause of morbidity and mortality in the aging population. An estimated 6.9 million Americans aged 65 and older live with AD in 2024, a number projected to increase to 13.8 million by 2060. AD inevitably progresses and patients die within an average of 4 to 8 years after diagnosis. Currently, there is no cure available. Therefore, there is an urgent need for novel therapeutic strategies. Emerging evidence suggests that semaglutide (Ozempic and Wegovy) and tirzepatide (Mounjaro and Zepbound), a new generation of GLP-1 receptor agonists (GLP-1RAs) approved for treating type 2 diabetes and weight loss, could offer a promising therapeutic approach for AD. Currently, two clinical trials (sponsored by Novo Nordisk) are ongoing to examine semaglutide in patients with early AD. No clinical trials are ongoing to test semaglutide in patients with later stages of AD. No clinical trials are ongoing for testing tirzepatide in AD. Additionally, mechanisms underlying potential therapeutic benefits of semaglutide and tirzepatide in AD remain largely unknown. Our proposal titled “Uncovering the Therapeutic Potential of Semaglutide and Tirzepatide in Alzheimer's Disease: Insights from Animal Models and Real-World Clinical Data” aims to address several critical but unanswered questions: 1) can semaglutide improve clinical outcomes in real-world patients with later stages of AD? 2) will tirzepatide offer similar or even more profound benefits in AD treatment? 3) which specific AD patients will benefit most? 4) what are the underlying mechanisms? This agile 3-year project will collect timely data on the therapeutic efficacy of semaglutide and tirzepatide across a wide range of clinical outcomes in real-world patients with AD, including those in later stages. It will identify which specific subgroups of AD patients are most likely to benefit from these treatments. This project will provide in-depth mechanistic insights into the effects of these drugs using AD transgenic mice. This research will complement and significantly expand upon existing clinical trials, offering robust real-world and mechanistic evidence to support the therapeutic benefits of semaglutide and tirzepatide that could move precision medicine approaches for AD drug discovery in a new direction.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $655,673 )
2026	2026	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Aging Research	000	1	8/13/2026	NEW	$655,673
														Subtotal = $655,673

Grand Total All Awards = $655,673

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Uncovering the Therapeutic Potential of Semaglutide in Alzheimer's Disease: Insights from Animal Models and Real-World Clinical Data

Award Number: R01AG099323

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/15/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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