On the one hand there is a modest amount of evidence for GLP-1 receptor agonist drugs to produce beneficial effects on an aged metabolism that are unconnected to weight loss. On the other hand, when Big Pharma has a very successful drug, it will attempt to use that drug for every condition it can that is associated with a sizable market, whether or not the expected effects are marginal. So it isn't necessarily indicative of support for these non-weight-loss mechanisms that leads the clinical trial of a weight loss drug for patients with Alzheimer's disease. Cynically, it is that Alzheimer's is an enormous market.
The present state of regulation makes it more cost-effective for companies to push existing drugs into new marginal uses than it is to develop new drugs that are actually effective for that new use. At times, it seems that the entire world cares nothing for how well a drug, a supplement, any intervention actually works at its given task. Effect sizes are boring, a dead letter. Drugs that do relatively little and only marginally slow progression of a condition are marketed aggressively and have huge sales. Big Pharma is far from the only culprit in this matter, of course. Just look at the supplement industry.
That a weight loss drug produces weight loss but at the same time fails to slow Alzheimer's disease might be taken as another data point to illustrate that the relationship between obesity and Alzheimer's disease is very different in character to, say, the robust and very direct relationship between obesity and type 2 diabetes. Yes, being overweight appears to be a risk factor that plays into Alzheimer's disease, but it isn't as strong a relationship, indicating a great deal more complexity and variation from individual to individual in the mechanisms involved.
Novo Nordisk today announced the top-line results from the 2-year primary analysis of evoke and evoke+ phase 3 trials in early-stage symptomatic Alzheimer's disease. The two trials were randomised, double-blinded, enrolled a total of 3,808 adults and evaluated the efficacy and safety of oral semaglutide compared to placebo on top of standard of care. The decision to pursue an Alzheimer's disease indication with semaglutide was based on real-world evidence studies, pre-clinical models as well as post-hoc analyses from diabetes and obesity trials.
The evoke and evoke+ trials did not confirm superiority of semaglutide versus placebo in the reduction of progression of Alzheimer's disease, as measured by the change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) score compared to baseline. While treatment with semaglutide resulted in improvement of Alzheimer's disease-related biomarkers in both trials, this did not translate into a delay of disease progression.
View the full article at FightAging
