Drug Discovery and Development

Liraglutide shows promise in lessening Alzheimer’s symptoms in phase 2b trial 

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Liraglutide, a GLP-1 receptor agonist medication that first won FDA approval in 2010, may reduce cognitive impairment in Alzheimer’s patients. At this year’s Alzheimer’s Association International Conference, data from a Phase 2b clinical trial with 204 mild AD patients serving as participants was revealed, showing that the drug lowered decline in cognition by up to 18% in the span of one year, a statistically significant difference (p<0.01).

In a similar manner to semaglutide, the active ingredient used in the blockbuster Ozempic/Wegovy, liraglutide is used to treat diabetes and obesity under the brand names Victoza and Saxenda, respectively. Novo Nordisk, the manufacturer of these two drugs, is also currently running clinical trials known as EVOKE and EVOKE Plus to investigate the potential impact of semaglutide on AD.

Interactive visualization of liraglutide supports zooming in and out as well as rotation. Data: “The 3D structure of Liraglutide (PDB ID: 4APD) (Steensgaard et al., 2013) was obtained from the RCSB Protein Data Bank (Berman et al., 2000).”

Semaglutide could be another therapy in the fight against Alzheimer’s

Alzheimer’s Disease has been dubbed by some researchers as “type 3 diabetes” because abnormal brain insulin resistance and a disruption in normal insulin signaling are correlated with AD. Insulin signaling in particular is vital in preserving the health and proper functioning of neurons, synapses, and glia. In addition, improper insulin signaling promotes the formation of the amyloid beta plaques that are the main pathology of AD according to the amyloid hypothesis. It remains to be seen whether semaglutide, liraglutide, or other GLP-1 receptor agonist drugs, will receive FDA approval for the treatment of AD. Some of the patents for liraglutide, an older GLP-1 drug, began expiring in late 2023.

Novo Nordisk announced in 2020 that an oral formulation of semaglutide would enter phase 3 development for Alzheimer’s disease. The trial remains active.

Semaglutide has also been examined by researchers studying rodent models of AD and found to have positive results. Wang et al. (2023) found that performance in learning and memory tasks, such as a novel object recognition test, was improved in 3xTG mice given semaglutide compared to control 3xTG mice. This finding was coupled with a reduction in amyloid and tau deposits and improvement in glucose metabolism in the brain. In humans, there is evidence suggesting that type 2 diabetes is a risk factor for cognitive decline, but GLP-1 receptor agonists, like semaglutide, can potentially mitigate this risk in people with type 2 diabetes.

An evolving treatment landscape for AZ

Currently, there are two FDA-approved monoclonal antibody drugs available for treating Alzheimer’s disease, including Lilly’s Kisunla (donanemab) and Eisai and Biogen’s lecanemab (Leqembi), which also decrease amyloid in the brain. Unlike Kisunla, however, GLP-1 receptor agonists do not carry the potential side effect of brain bleeds or swelling.

Emma San Filippo graduated from Vassar College with a Bachelor of Arts in Neuroscience and Behavior. During her time at Vassar, she was a General and Lay Editor for the college’s chapter of the Grey Matters Journal, a student-run neuroscience publication. 

References

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Filed Under: Brain Breakthroughs, clinical trials, Drug Discovery, Neurological Disease
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