GLP-1 receptor agonists, primarily approved for type 2 diabetes and obesity, are emerging as potential treatments for other diseases, including Alzheimer’s. Christian Hölscher of Kariya Pharmaceuticals highlighted the hormone’s diverse effects in the body and its untapped potential. GLP-1, besides regulating insulin secretion and glucose uptake, is also produced in the central nervous system, notably the brainstem. Given that the brain consumes about 20% of the body’s energy, Howard Fillit from the Alzheimer’s Drug Discovery Foundation emphasized the relationship between aging, insulin resistance, and glucose deprivation in brain regions tied to learning and memory.

Some experts call Alzheimer’s “type 3 diabetes” due to the role of insulin resistance. A 2022 review in Frontiers in Endocrinology1 speculated that GLP-1-targeting drugs for diabetes might be repurposed for Alzheimer’s. Early research showed that GLP-1 receptor agonists can mitigate neuroinflammation and oxidative stress, two key contributors to Alzheimer’s. Recent results from the Phase II ELAD study, funded by ADDF, revealed that Novo Nordisk’s liraglutide slowed the progression of Alzheimer’s in patients, compared to a placebo. In 2021, Novo Nordisk initiated two Phase III trials, EVOKE and EVOKE Plus, with outcomes expected by September 2025.

However, Christian Hölscher, co-founder and chief scientific officer at Kariya Pharmaceuticals, pointed out the challenge of current drugs like liraglutide and semaglutide, which are primarily designed to remain in the bloodstream, thus restricting their potential in brain diseases. Kariya has developed drugs that can penetrate the brain, offering better effects in preclinical studies. A psychological barrier exists, with Alzheimer’s experts unfamiliar with GLP-1 and vice versa for diabetes researchers. Despite this, the advantages of GLP-1 drugs are evident: proven safety, easy administration, and the possibility of combining them with anti-amyloid drugs like Leqembi and donanemab. In combination trials, Leqembi and donanemab have shown significant reductions in Alzheimer’s progression. While these are remarkable breakthroughs, the ultimate goal remains a complete slowdown or prevention of the disease.

References:
1.The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer’s disease. Du H, Meng X, Yao Y, Xu J. Front Endocrinol (Lausanne). 2022 Nov 17;13:1033479. doi: 10.3389/fendo.2022.1033479. eCollection 2022.
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