All GLP-1 Agonists Should, Theoretically, Cure Alzheimer’s Dementia but Dulaglutide Might Be More Effective Than the Others

Abstract

Addressing the dysfunctions of all brain cell types in Alzheimer’s disease (AD) should cure the dementia, an objective that might be achieved by GLP-1 agonist drugs, because receptors for GLP-1 are present in all of the main brain cell types, i.e., neurons, oligodendroglia, astroglia, microglia, endothelial cells and pericytes. This article describes the benefits provided to all of those brain cell types by GLP-1 agonist drugs. The article uses studies in humans, not rodents, to describe the effect of GLP-1 agonists upon cognition, because rodents’ brains differ from those of humans in so many ways that results from rodent studies may not be totally transferable to humans. Commercially available GLP-1 agonists have mostly shown either positive effects upon cognition or no effects. One important reason for no effects is a reduced rate of entering brain parenchyma. Dulaglutide has the greatest entry to brain, at 61.8%, among the available GLP-1 agonists, and seems to offer the best likelihood for cure of AD. Although there is only one study of cognition that used dulaglutide, it was randomized, placebo controlled, and very large; it involved 8828 participants and showed significant benefit to cognition. A clinical trial to test the hypothesis that dulaglutide may cure AD should have, as its primary outcome, a 30% greater cure rate of AD by dulaglutide than that achieved by an equipoise arm of, e.g., lithium plus memantine.