Liraglutide may slow cognitive decline, brain volume loss in patients with AD dementia

Key takeaways:

• Research suggests liraglutide reduced cognitive decline by as much as 18% after 1 year of treatment compared with placebo.
• Those in the treatment cohort had nearly 50% less brain volume loss vs. those in the placebo cohort.

PHILADELPHIA — Treatment with liraglutide appeared to reduce cognitive decline and slow volume loss in several areas of the brain after 1 year among individuals with mild to moderate Alzheimer’s dementia, according to new research.

“Preclinical evidence in transgenic models of Alzheimer’s disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalizing synaptic plasticity and cerebral glucose uptake and increasing the proliferation of neuronal progenitor cells,” Paul Edison, MD, PhD, lead study author and professor of neuroscience at Imperial College London, and colleagues wrote.

Researchers aimed to assess the safety, efficacy and tolerability of liraglutide (Novo Nordisk) — a glucagon-like peptide-1 analogue — in a double-blind, placebo-controlled, phase 2b clinical trial of patients with mild to moderate Alzheimer’s dementia at 24 sites in the United Kingdom.

Edison and colleagues enrolled 204 patients, who were randomly assigned 1:1 to receive a daily subcutaneous injection of liraglutide or placebo for 12 months. Researchers performed MRI brain scans and fluorodeoxyglucose F18 positron emission tomography at baseline, then again at 12 months, along with clinical assessments and neuropsychometric evaluations at regular intervals.

Study participants also underwent cognitive testing at baseline and at weeks 24 and 52, with cognitive function assessed as a composite score of 18 tests for memory, comprehension, language and spatial orientation.

Researchers repeated scans on all individuals who completed 52 weeks of treatment and evaluated volumetric changes from baseline via both regional volume and voxel-based morphometric analyses.

According to results, 79 patients on liraglutide and 87 on placebo completed 52 weeks of treatment, and those on liraglutide demonstrated up to an 18% reduction in cognitive decline at this time point compared with those on placebo.

Data further showed that those in the liraglutide cohort had nearly 50% less volume loss in frontal, temporal, parietal and total gray matter, as measured by MRI, vs. those on placebo.

Researchers noted that gastrointestinal issues were the most commonly reported adverse events, reported in around one-fourth of liraglutide-treated patients (25.5%). Twenty-five serious side effects were reported in 18 participants from the placebo arm and seven participants in the treatment arm, most of which were unlikely to be treatment-related.

“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” Edison said in a related release. “While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid-beta and tau, and improving how the brain’s nerve cells communicate.”

Reference:

• GLP-1 drug liraglutide may protect against dementia. https://aaic.alz.org/releases-2024/glp-drug-liraglutide-may-protect-against-dementia.asp. Published July 29, 2024. Accessed July 30, 2024.