Tirzepatide May Offer Neuroprotective Benefits Against Alzheimer's and Dementia: Study

Tirzepatide is a dual agonist of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptors. Initially approved for managing type 2 diabetes (T2D) and obesity, tirzepatide has shown additional potential in targeting disease mechanisms associated with Alzheimer’s disease (AD).

It is well documented that T2D and obesity contribute to systemic low-grade inflammation and oxidative stress, which in turn can trigger neuroinflammation and oxidative damage in the brain. These processes are recognized as contributing factors in the onset and progression of AD, the most prevalent neurodegenerative condition and a leading cause of dementia worldwide.

The review highlights that tirzepatide’s ability to mitigate systemic inflammation and oxidative stress may offer protective effects against the development of AD pathology. Specifically, tirzepatide may inhibit amyloid-beta (Aβ) production, which is central to the formation of amyloid plaques seen in AD. Furthermore, tirzepatide could help reduce associated neuroinflammation, oxidative stress, and neuronal cell death.

Tirzepatide’s impact extends to modulating mechanisms linked to brain metabolism. The review notes that the drug can improve brain leptin sensitivity, potentially breaking the connection between obesity and AD. Additionally, it stimulates adiponectin expression, further contributing to a healthier metabolic profile in patients with T2D and obesity.

On a molecular level, tirzepatide is believed to influence several signaling pathways involved in neuronal survival and function, including PI3K/AKT, GSK3β, BDNF, and CREB pathways. It also affects microRNAs such as miR-212-3p and miR-43a-5p, which are involved in neurogenesis and neuronal differentiation.

Through these mechanisms, tirzepatide helps counteract the harmful effects of chronic hyperglycemia and excess body weight on brain health, potentially slowing the onset and progression of AD. The review underscores that tirzepatide works both peripherally — by reducing systemic inflammation and oxidative stress — and centrally — by protecting neurons and preserving cognitive function.

Despite these promising insights, the authors caution that most evidence for tirzepatide’s neuroprotective effects comes from preclinical studies. As such, there remains a significant need for well-designed clinical trials to validate these findings in human populations.

The authors conclude, "Tirzepatide represents an exciting avenue for future research into AD treatment, offering hope that this antidiabetic and anti-obesity agent could also help combat the growing burden of dementia."

Reference:

Alshehri, G.H., Al-kuraishy, H.M., Waheed, H.J. et al. Tirzepatide: a novel therapeutic approach for Alzheimer’s disease. Metab Brain Dis 40, 221 (2025). https://doi.org/10.1007/s11011-025-01649-z