Novo Nordisk

A potential new treatment approach

Oral semaglutide is a type of medicine called a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that is currently approved for the treatment of type 2 diabetes^7,9* and with a well-established safety profile.^10,11

The journey of investigating GLP1 RAs in Alzheimer’s disease began 20 years ago with the first studies of GLP1-RAs in neuronal protection¹⁰. Since then, results have emerged showing a potential benefit in people with Alzheimer’s disease^11-14, which we are now further investigating with semaglutide in early Alzheimer’s disease^{8, 9}.

Semaglutide is thought to work in a number of ways, including affecting nerve cells, as well as other cell types. This may result in an overall improvement of nerve cells, inflammation and vascular health that could potentially help to slow the clinical progression of Alzheimer’s disease.^15-17

Although the pathology of Alzheimer’s disease is very complex and there is a lot still to understand about the disease, we know that neuroinflammation is a pathophysiological feature that plays a key role.^{7, 18} Evidence suggests that, over time, chronic inflammation in the brain could result in the inability of neurons to communicate, and eventually die.¹⁹ Other factors that may play a role in the cause of Alzheimer’s disease include changes in the finely regulated blood supply to the brain, leading to failure to deliver enough nutrients to the brain.⁷

Novo Nordisk’s hope for the future

Alzheimer’s disease has been an area of increasing and extensive research over the past few decades, but progress in research and development is challenging due to the complexity and limited knowledge of the brain.

Novo Nordisk is committed to investing in this area to help people diagnosed with Alzheimer’s disease live longer, with dignity, and with meaningful relationships. With the initiation of the evoke and evoke+ trials, Novo Nordisk will explore a potential treatment to slow the disease progression in people with early Alzheimer’s disease.

References

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7. Association As. Alzheimer’s Disease Facts and Figures. 2021;17.
8. ClinicalTrials.gov. A Research Study Investigating Semaglutide in People With Early Alzheimer’s Disease (EVOKE). https://clinicaltrials.gov/ct2/show/NCT04777396. Last accessed: June 2021.
9. ClinicalTrials.gov. A Research Study Investigating Semaglutide in People With Early Alzheimer’s Disease (EVOKE Plus). https://clinicaltrials.gov/ct2/show/NCT04777409. Last accessed: June 2021.
10. Perry T, Haughey NJ, Mattson MP, et al. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J Pharmacol Exp Ther. 2002;302:881-8.
11. During MJ, Cao L, Zuzga DS, et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003;9:1173-9.
12. Gejl M, Brock B, Egefjord L, et al. Blood-Brain Glucose Transfer in Alzheimer’s disease: Effect of GLP-1 Analog Treatment. Sci Rep. 2017;7:17490.
13. Jansen IE, Savage JE, Watanabe K, et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat Genet. 2019;51:404-413.
14. Zhao L, Li Z, Vong JSL, et al. Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain. Nat Commun. 2020;11:4413.
15. Rakipovski G, Rolin B, Nøhr J, et al. The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE(-/-) and LDLr(-/-) Mice by a Mechanism That Includes Inflammatory Pathways. JACC Basic Transl Sci. 2018;3:844-857.
16. Aroda VR, Rosenstock J, Terauchi Y, et al. PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. Diabetes Care. 2019;42:1724-1732.
17. Rodbard HW, Rosenstock J, Canani LH, et al. Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial. Diabetes Care. 2019;42:2272-2281.
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19. Scahill RI, Schott JM, Stevens JM, et al. Mapping the evolution of regional atrophy in Alzheimer’s disease: unbiased analysis of fluid-registered serial MRI. Proc Natl Acad Sci U S A. 2002;99:4703-7.