Evaluating the effects of the novel GLP-1 analogue, liraglutide, in patients with Alzheimer’s disease: an RCT (ELAD Study). | C4C

Type 2 diabetes mellitus (T2DM) has been identified as a risk factor for Alzheimer’s disease (AD). In T2DM, insulin signalling is impaired, and it has been shown that insulin signalling is desensitised in the brains of people with AD. Apart from the control of blood glucose, insulin has the general physiological profile of a growth factor. The neuronal insulin receptors have been shown to induce dendritic sprouting, neuronal stem cell activation, and general cell growth, repair Furthermore, insulin and the related insulin-like growth factor (IGF-1) are potent neuroprotective factors. Liraglutide specifically has been shown to be neuroprotective in in vitro cell models of AD and has improved behavioural outcomes, brain metabolism on FDG PET and pathological burden of both amyloid and p-tau in transgenic animal studies. Based upon this pre-clinical data, liraglutide emerged as the best candidate for repositioning as a treatment for AD from a recent systematic review in Nature Reviews Drug Discovery.