Alzheimer’s Disease affects over 7 million people in the United States, with approximately 1 in 9 patients aged 65 and older having the condition and most patients being female. The disease results from buildup of amyloid-beta plaques and tau neurofibrillary tangles, leading to neuroinflammation, synaptic dysfunction, and eventual neuronal death.
Current FDA-approved treatments for Alzheimer’s include cholinesterase inhibitors (donepezil, rivastigmine, and galantamine), memantine, and newly approved anti-amyloid drugs (lecanemab and donanemab). Donepezil is indicated for all stages of the disease, while rivastigmine and galantamine only manage mild and moderate stages. Memantine is typically added in moderate-to-severe stages. Combination treatment of memantine and donepezil in moderate to severe AD has been observed to reduce disease progression with tolerable adverse effects. The newer anti-amyloid drugs are intravenous infusions or subcutaneous injections requiring patients to meet specific criteria and undergo frequent MRIs to monitor for brain hemorrhage risk.
GLP-1 agonists—popular as weight-loss medications and for managing type 2 diabetes—have been studied for neuroprotective potential in Alzheimer’s because diabetes and obesity are possible risk factors for the disease. Animal models showed possible mechanisms including reductions in inflammation and oxidative stress. However, recent phase 3 clinical trials enrolling 4000 patients with early AD who received daily oral semaglutide for approximately 2 years did not demonstrate benefits. The semaglutide was unable to cross the brain at a dosage sufficient to enhance neuroprotection, and it remained unclear how far patients had progressed in neurodegeneration when starting treatment.
Future research will evaluate whether newer dual and triple agonists or small-molecule oral GLP-1 agonists can better penetrate the brain to reduce neurodegeneration. Alternative approaches under consideration include intranasal routes of administration and drug nanoparticles. Researchers will also work to identify which patients have the greatest potential to benefit from neuroprotection with these drugs and whether combining incretins with other medications can enhance efficacy with minimal adverse effects.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.pharmacytimes.com/view/glp-1-agonists-as-therapeutics-for-alzheimer-s-disease-not-right-now-but-maybe-in-the-future