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AAIC 2021 | Phase IIb ELAD trial of liraglutide in mild-moderate Alzheimer’s disease
Paul Edison, MD, PhD, MPhil, FRCP, FRCPI, Imperial College London, London, UK, discusses findings from the ELAD study (NCT01843075), a 12-month randomized, placebo-controlled trial investigating the efficacy of liraglutide in patients with mild to moderate Alzheimer’s disease. Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue used for the treatment of type 2 diabetes, exhibited neuroprotective effects in transgenic models of Alzheimer’s. A total of 204 patients were recruited and randomized 1:1 to either receive a daily injection of liraglutide or placebo. [18F]FDG-PET and MRI brain scans were performed at baseline and following treatment to assess the change in cerebral glucose metabolic rate in cortical regions. The study demonstrated that liraglutide treated patients performed significantly better than placebo in cortical MRI volume, showing statistically significantly less deterioration. Additionally, patients treated with liraglutide showed significantly better cognitive function scores compared to placebo (ADAS-EXEC). No significant change in glucose metabolism was observed. This interview took place during the Alzheimer’s Association International Conference 2021.
Transcript (edited for clarity)
Liraglutide is a GLP-1 analog. It’s an anti-diabetic drug. What we and others have shown is that in the preclinical model, it has reduced the neuroinflammation, tau formation. It improves the synaptic function, it reduces the amyloid formation, and overall it improved the neuronal function and memory in animal models. This is also demonstrated in very small numbers of human subjects. It’s not only in Alzheimer’s disease that the GLP-1 analog as a class of drug has been tested in Parkinson’s disease...
Liraglutide is a GLP-1 analog. It’s an anti-diabetic drug. What we and others have shown is that in the preclinical model, it has reduced the neuroinflammation, tau formation. It improves the synaptic function, it reduces the amyloid formation, and overall it improved the neuronal function and memory in animal models. This is also demonstrated in very small numbers of human subjects. It’s not only in Alzheimer’s disease that the GLP-1 analog as a class of drug has been tested in Parkinson’s disease. And it has also shown some improvement in Parkinson’s disease patients.
Based on all the preclinical evidence with liraglutide, the aim of the ELAD study, which is Evaluation of Liraglutide in Alzheimer’s Disease, was to see how the liraglutide works in Alzheimer’s disease, and more importantly, whether it changes glucose metabolism in the treatment group compared to the placebo, and also whether it causes any changes in the MRI, and more importantly cognitive function. So in this particular study we recruited around 204 patients. They were randomized one-to-one to receive either treatment or placebo. The subjects had a daily injection of liraglutide, and the patients had the baseline MRI and PET scan all done at a single center, at Imperial College London. Then the patients underwent the clinical visits, which were done locally, and finally, they had the final MRI and PET scan again at the same scanner at Imperial College London.
So what we have demonstrated is that patients who were treated with liraglutide, they tolerate the drug very well, and more importantly, the MRI volume was maintained in the patients treated with the liraglutide, while those who didn’t receive the active treatment, the MRI volume was deteriorated significantly compared to the treatment arm. Again, looking at the cognitive function, the cognitive function also performed much better in patients who were treated with the liraglutide compared to the placebo. However, we did not see a significant change in the glucose metabolism, which we think is probably because of the small numbers studied in the subject.
So I think it is a rather small study. Even though we had 200 subjects, 200 subjects are not really enough to demonstrate the efficacy of the drug. However, we were able to show that it has improved the cognitive function, which was actually an excellent finding considering the small number of patients. We were also shown that the biomarker, the MRI has also improved, or was better in the patients treated with the liraglutide, which suggests that a larger study looking at the GLP-1 analog has got great potential, and could be a treatment in Alzheimer’s disease if we were to prove that it improves the cognitive function in larger studies.
There are oral GLP-1 analogs at the moment. Novo Nordisk, who is the company which produces this compound, they are already trying to run a Phase III study of the oral GLP-1 analog.