Alzheimer's Disease: The Promise of Diabetes Drugs

Current pharmacologic interventions in Alzheimer's disease (AD) have limited effectiveness.

Most of the current AD drugs available promise to slow the rate of progression but fail to reverse or prevent the disease.

Novel strategies for AD drug treatment are desperately needed and one promising class of agents are the newer drugs for treatment of diabetes. 

How might a diabetes treatment drug potentially treat a brain disease like AD?

A recent review article in World Journal of Diabetes summarizes what is known about the neuroprotective effect of the anti-diabetic drug liraglutide (trade name Saxenda in the U.S.). This review article is extensive but I will try to summarize the key points.

1. Long-acting glucagon-like peptide-1 (GLP-1) is a naturally occuring peptide known to promote insulinotropic activity and glucose homeostasis
2. GLP-1 is primarily excreted in the gut but receptors for the compound are found throughout the body including the brain.
3. GLP-1 is a key component of the gut-brain axis and along with the vagal nerve helps regulate energy metabolism, insulin secretion, appetite and weight control.
4. Liraglutide is a recently approved GLP-1 receptor agonist with an effect similar to naturally occuring GLP-1.
5. Liraglutide along with regulating glucose in type 2 diabetes has brain anti-inflammatory, anti-oxidant, microglia inhibition and neuroprotective actions.
6. Higher doses of liraglutide promote weight loss and the drug has recently been approved for weight loss in the U.S.
7. Preclinical trials suggest liraglutide may improve cognitive function in AD and may have beneficial effects on AD biomarkers such as beta amyloid brain levels.
8. Future research combining liraglutide with dipeptidyl peptidase-4 (DPP-4) inhibitors may lead to a "therapeutic dream team" combination for both diabetes and neurodegenerative diseases including AD
9. Basic research suggests brain insulin resistance is a key mechanism in AD and other central neurodegenerative disorders. Brain insulin resistance may be reduced or eliminated by the use of centrally acting anti-diabetic drugs like liraglutide.
10. Preclinical studies also find evidence that liraglutide "modulates synaptic plasticity by enhancing long-term potentiation" and improves learning an memory in rat models of AD.

This review makes some quite remarkable predictions about the potential for GLP-1 drugs in brain disorders including AD. Whether these predictions will be true is yet to be seen.

Certainly we can expect to see more research using anti-diabetic drugs in AD and other brain diseases.

Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link below.

Photo of great egret is from the author's files.

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Candeias EM, Sebastião IC, Cardoso SM, Correia SC, Carvalho CI, Plácido AI, Santos MS, Oliveira CR, Moreira PI, & Duarte AI (2015). Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide. World journal of diabetes, 6 (6), 807-27 PMID: 26131323