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Dementia is one of the conditions that render the hope of a long and healthy lifespan elusive for many people. Estimates suggest that as many as 20% of people over the age 65 suffer from cognitive impairment1, which is defined as the early prodromal stage of dementia. Of these, around one-third develop dementia within 5 years2. Dementia is often due to Alzheimer’s disease (AD), which affects more than 50 million people globally3, 4.

There is a well-known link between dementia, including AD, and type 2 diabetes (T2D) as a factor that markedly increases the risk of developing dementia5. Given this association, Novo Nordisk - as a company devoted to defeat diabetes and other serious chronic diseases - has recently begun exploring whether glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) may be beneficial as a novel treatment option in Alzheimer’s disease. All approved GLP-1 RAs are currently used to improve glycaemic control in T2D, and some are also used for weight management.

Hitherto, therapeutic options in AD have been very sparse and management of the disease has focused on symptomatic relief. Further complicating matters, there remains a profound lack of efficient diagnostic and prognostic modalities, severely challenging the possibility of timely intervention to stop the progressive neurodegeneration characterising AD.

Below, we introduce a recent article that details data analyses to assess how treatment with liraglutide and semaglutide impact the risk of dementia in people with T2D. These results and other evidence led to the initiation of the ongoing evoke and evoke+ phase 3 trials in AD, which are also introduced.

To study the impact of GLP-1 RA treatment on the risk of dementia in people with type 2 diabetes, two large cohorts were analysed by Nørgaard and colleagues as reported in Alzheimer’s & Dementia . In a cohort based on data pooled from three CVOTs with liraglutide or semaglutide, the rate of dementia was shown to be 53% lower in trial participants randomised to semaglutide or liraglutide (hazard ratio [HR] vs placebo of 0.47; 95%CI: 0.25 to 0.86). In a cohort based on a nation-wide Danish register, the HR was 0.89 (95%CI: 0.86-0.93) in individuals with increasing GLP-1 RA exposure vs. those on other second-line diabetes therapeutics.


The article is accompanied by an illustrative synopsis that presents highlights of the study.

Two phase 3 randomised clinical trials are currently ongoing with oral semaglutide to test if this GLP-1 RA for oral administration in a tablet provides benefits in early-stage Alzheimer’s disease (mild cognitive impairment and mild dementia). The 104-week trials, which are planned to report in the second half of 2024, are the first large-scale trials to formally test the hypothesis. In the trials, a wide array of outcomes and parameters are assessed; moreover, substudies are also included, for example to improve the understanding of the mechanisms of action of GLP-1 RA treatment in AD. 


The presentation was given at the 2021 Conference Clinical Trials on Alzheimer’s Disease (CTAD), the abstracts of which are available in The Journal of Prevention of Alzheimer’s Disease (abstract #OC01, page S13).


Clin Geriatr Med. 2013;29:753-772


Dement Geriatr Cogn Dis Extra. 2013;3:320-332 


The Alzheimer's Disease International. World Alzheimer Report 2015. Global Impact of Dementia


Nat Rev Dis Primers. 2021 May 13;7(1):33; [5] Lancet Diabetes Endocrinol. 2020;8:535-545.


Lancet Diabetes Endocrinol. 2020;8:535-545.