Reacción a "Oral semaglutide does not slow the progression of Alzheimer's disease, according to a trial"

The EVOKE and EVOKE+ studies were based on the hypothesis that the semaglutide-mediated impact on neuroinflammation could reduce disease progression in patients with Alzheimer’s disease (AD). Real-world evidence with semaglutide indicated that its use in patients with type 2 diabetes was associated with a lower risk of dementia, suggesting possible neuroprotective effects beyond glycemic control. These findings provided an important basis for further investigating semaglutide as a strategy to reduce dementia risk.

Metabolic conditions in midlife, such as obesity and diabetes, are well-established and modifiable risk factors for the development of dementia (as highlighted by the Lancet Commission on dementia risk factors). Excess adiposity and impaired glucose metabolism contribute to chronic inflammation, vascular dysfunction, and other pathophysiological mechanisms involved in neurodegeneration and cognitive decline. Taken together, this evidence supports evaluating semaglutide as a therapeutic approach to mitigate dementia risk and improve long-term brain health.

In the EVOKE studies, the mean age was 72.2 years. One could hypothesize that these interventions should be applied earlier in life. At the same time, since not all participants tolerated the highest dose of 14 mg and consequently received 3 or 7 mg during the study, a better understanding of the relationship between dosage and changes in Alzheimer’s disease biomarkers would help interpret the results more accurately. The 14 mg oral dose is equivalent to a weekly subcutaneous administration of 0.5 mg.

Finally, these patients were amyloid-positive, and it may be necessary to combine amyloid clearance with treatment using GLP-1 agonists to observe an effect. Alternatively, these treatments might be effective at earlier stages, in patients at higher risk of amyloid accumulation, before amyloid and tau build up in the brain.