All-Purpose Drugs: GLP-1s Offer Hope in Neurodegenerative Disease

Glucagon-like peptide-1 receptor agonists (GLP-1) have emerged as a beacon of hope for the millions of people worldwide living with obesity and type 2 diabetes (T2D). These serious diseases have become global public health issues in the last three decades – the result of urbanization, sedentary lifestyle, and increased consumption of high-calorie processed foods. Obesity affects one in three adults and one in six children in the United States, and worldwide, more than 1 billion people are obese, according to the World Health Organization. T2D was responsible for more than one million deaths in 2017, ranking it as the ninth leading cause of mortality.

13 GLP-1 drugs have received FDA approval, starting with Victoza (liraglutide) for T2D in 2010, and most recently for Zepbound (tirzepatide) for obesity in 2023. Ozempic, arguably the most well known of the GLP-1 set, is approved for use in T2D and seeking an expanded label for the treatment of obesity. Along with T2D and obesity, these drugs have shown to reduce the risk of heart attack, stroke, and other major adverse cardiovascular events (MACE),  and according to recent studies, they may also have applications in the treatment of neurodegenerative disease.

According to a 2022 research report published in ScienceDirect, GLP-1 drugs have been shown to have anti-inflammatory, neurotrophic, and neuroprotective properties in neurodegenerative disorder preclinical models, and hold promise for repurposing as a treatment for neurodegenerative diseases. Chronic inflammation is a key feature of diseases including Alzheimer’s and Parkinson’s diseases, but to date, neuroinflammatory pathways have not been targeted in clinical treatments for these diseases.

This week, the New England Journal of Medicine published details of a clinical trial that evaluated lixisenatide, a first generation GLP-1, as a potential treatment for early onset Parkinson’s disease. Encouragingly, the Phase 2, double-blind, randomized, placebo-controlled trial showed that lixisenatide therapy resulted in less progression of motor disability than placebo at 12 months.

Novo Nordisk also sees the potential benefits of these drugs in the treatment of neurodegenerative disease. The company is studying the role of semaglutide in mitigating the cognitive effects of Alzheimer’s disease, which affects nearly seven million Americans, and is expected to have an economic burden of over $1 trillion by 2050. Novo’s candidate, NN-6535, is administered in oral tablet form and via subcutaneous injection and is the subject of two pivotal trials – evoke and evoke+ – which commenced in 2021 and will assess changes in cognition and function and compare the effects on slowing clinical progression to dementia in people with mild cognitive impairment.

Longer and larger trials will be needed to determine the safety and efficacy of GLP-1 drugs in treating neurodegenerative disease, but there is hope on the horizon.

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All-Purpose Drugs: GLP-1s Offer Hope in Neurodegenerative Disease

Catie Corcoran

Biotech Editor