How liraglutide works
Alzheimer’s disease is a neurological disorder where the slow death of nerve cells in the brain results in a progressive decline in memory and thinking ability. Patients have abnormal brain metabolisms, which can include changes in glucose metabolism that is controlled by the hormone insulin. Glucose is essential for cell survival as it is used to produce energy. Decreased glucose levels is common in the brains of Alzheimer’s patients and is associated with cell death and memory loss as shown in studies using animal models of the disease.
Liraglutide is an analog of glucagon-like peptide 1 (GLP-1), a hormone that stimulates insulin signaling. Increased insulin signaling is thought to improve the transport of glucose in the brain and potentially reduce nerve cell death (neurodegeneration).
Liraglutide in clinical trials
Liraglutide is currently being studied in clinical trials involving Alzheimer’s disease patients. A clinical trial (NCT01469351) in 38 patients compared the effect of liraglutide versus a placebo over a six-month period, and was completed in 2013. The results, published in the scientific journal Frontiers in Aging Neuroscience showed potentially promising effects of the treatment on glucose metabolism. The placebo group displayed a significant reduction in glucose metabolism across several brain regions, whereas patients treated with liraglutide maintained levels similar to those at the start of the trial. No significant benefit was seen in other measures, such as thinking ability, but this could be due to the short trial period, small number of patients, and varying disease stages of the participants.
A randomized, double-blind, placebo-controlled Phase 2 trial (NCT01843075), called ELAD, is aiming to assess the effect of liraglutide in an estimated 206 patients with mild (early-stage) Alzheimer’s disease over a 12-month period in the U.K. The trial will assess the hallmarks of Alzheimer’s progression, such as amyloid plaque formation and tau deposits in the brain, in patients treated with liraglutide compared with those treated with a placebo. The trial is active but no longer recruiting patients, and is estimated to be completed in December 2019.
Results from a 12-week study of liraglutide in 43 healthy, middle-aged participants showed no real differences in cognitive ability between liraglutide and placebo groups. However, the study did find improved connectivity between parts of the brain called the default mode network when comparing the two groups. Alzheimer’s patients are known to have decreased function in the default mode network.
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