Commentary
Video
Glucagon-like peptide-1 (GLP-1) analogs demonstrate potential to address multiple pathological processes in Alzheimer disease, with promising early research suggesting cognitive improvements and potential for future treatment.
In an interview with Pharmacy Times®, Paul Edison, MBBS, PhD, FRCPI, professor of neurology at Imperial College London, discusses the potential of GLP-1 analogs in treating Alzheimer disease (AD), highlighting their unique ability to target multiple pathological processes, including tau formation, insulin resistance, and synaptic dysfunction. The discussion was based on Edison's presentation "GLP-1 Receptor Agonists: A Panacea or Too Good to Be True?" during the "Hot Topics in Neurology" plenary session on Saturday, April 5, at the American Academy of Neurology (AAN) 2025 Annual Meeting in San Diego, California.
Edison's research with liraglutide (Victoza; Novo Nordisk) showed cognitive improvements in non-diabetic AD patients, and he predicts these medications could become as transformative for neurodegenerative conditions as statins were for cardiovascular disease. Edison explains how pharmacists and treatment providers could potentially play a role in implementing future results garnered from ongoing research into GLP-1s and their association with improved AD outcomes.
Pharmacy Times: Could you elaborate on how GLP-1s can provide neurocognitive effects against Alzheimer disease?
1. GLP-1 analogs can potentially address multiple pathological processes in AD simultaneously
2. Early studies show cognitive improvements in patients treated with GLP-1 analogs
3. Future research needs to focus on developing brain-penetrating, oral formulations of these medications
Paul Edison, MBBS, PhD, FRCPI: If you were to look at AD, there are different pathological processes happening. Apart from the amyloid, there is tau formation, astrocyte activation, insulin resistance, mitochondrial dysfunction, synaptic dysfunction, and reduced glucose metabolism that all could lead to atrophy. If you were to have an effective treatment, you would need to target all these pathological processes either by multiple drugs or by a single drug. If you were to look at the mechanism of action of GLP-1 analogs, it has got a unique mechanism by which it influences tau formation, insulin resistance, synaptic dysfunction, microglial activation, and astrocyte dysfunction. By the combination of these effects, GLP-1 analogs have the potential to be a beneficial treatment for AD.
Pharmacy Times: How can this research into GLP-1s pan out into future recommendations for managing AD?
Edison: We've got plenty of data coming out. We also have done a study where we looked at liraglutide, a GLP-1 analog, in around 200 patients who are non diabetic AD patients. What we have demonstrated is there is improvement in the cognition, as well as improvement in the MRI volume, in patients who were treated with liraglutide compared to the placebo. There's several natural history studies, ie, based on the database, observation studies, where you can see that the GLP-1 analogs clearly reduces incidence of dementia. However, we need much larger prospective studies to evaluate this, but my feeling is that these GLP-1 analogs have the potential to prevent and treat AD. It is likely going to be an add-on treatment along with whatever other existing treatment, including anti-amyloid agents. With the new GLP-1 analogs coming along, which are oral, they are much easier to take than the daily or weekly injections. It is going to clearly revolutionize the field once we are able to demonstrate these drugs are effective, and my feeling is that in a few years time, it would be like a statin for cardiovascular disease, with the majority of the people likely to be on one or another form of GLP-1 analogs.
Pharmacy Times: What is the future for this research as you continue to study this relation to AD and other neurocognitive conditions?
Edison: We now know that the GLP-1 analogs have got some effect on the brain. We also know that some of these GLP-1 analogs do not cross the blood-brain barrier. We also have got conflicting studies. Some of the studies in Parkinson disease were successful, some of the studies were failures, and most of these studies are of a relatively small number of subjects. We clearly need to evaluate these agents in a much larger population. More importantly, we need to also look at agents which can cross the blood-brain barrier. Even though these GLP-1 analogs can have an effect because of its peripheral function, are you reducing the cardiovascular risk by themselves? It can have an effect, by reducing the obesity, insulin resistance, improving the cardiovascular function, reducing the stroke [risk], atherosclerosis, and so on; but having an agent which is able to get into the brain and have much more impactful effect on the neurons will be be essential. The field will be looking at having brain-specific agents, which are also oral agents, which can be taken by millions of patients.
