Health and Medicine
PUBLISHED
GLP-1s aren't just for weight loss. That’s not even what they were approved for in the first place, but it’s what most people know them for.
Following the boom in popularity of these drugs, and brands like Ozempic becoming household names, lots of scientific studies have suggested they could have many more uses than we may have realized.
One suggestion that dates back a few years is that they could play a role in slowing the progression of Alzheimer’s disease. Recent trials have produced conflicting results – so, what’s the deal?
The GLP-1 revolution
To give them their full name, glucagon-like peptide-1 receptor agonists work by interacting with GLP-1 receptors, which are expressed by many different cells within the body.
Glucagon-like peptide-1 is a hormone the body naturally produces that boosts insulin production. GLP-1 drugs have the same effect because they act on the same receptors, which is what makes them work as treatments for type 2 diabetes.
The fact they can also be used as weight-loss aids emerged later and is what has catapulted them to fame.
There have also been strong hints that they may have yet more undiscovered effects.
These include benefits such as improving fertility in men with low testosterone related to obesity, a possible decrease in the risk of certain cancers, and even tempering violent behavior.
But there are also potential negative effects. That same study on cancer found the drugs may increase the risk of kidney cancer, for example, and another recent study found they could trigger anhedonia and cause “emotional flatness.”
There are also the known side effects that can come with taking these drugs, which affect people to varying degrees – from mild short-term nausea and gastric upset to gallstones and pancreatitis.
A large study in early 2025 aimed to catalog what was known about GLP-1 off-target effects up to that point. One was a possible decreased risk of Alzheimer’s disease and other forms of dementia.
A mixed bag of evidence
Studies suggesting a potential positive impact of GLP-1s on Alzheimer’s risk date back to long before we’d ever heard that infuriating Ozempic commercial jingle.
In 2018, a study in mice found that a combination therapy targeting three receptors, including the GLP-1 receptor, had a positive impact on memory loss and Alzheimer’s-associated brain pathology.
Liraglutide, a GLP-1 drug available under the brand name Saxenda for the treatment of obesity, also has some promising evidence behind it as a potential treatment for Alzheimer’s.
A recent clinical trial led by scientists at Imperial College London tested liraglutide in patients with Alzheimer’s for one year and found it could reduce cognitive decline by as much as 18 percent.
“We think liraglutide is protecting the brain possibly by reducing inflammation, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers or improving how the brain’s nerve cells communicate,” commented study lead Professor Paul Edison in a statement at the time.
However, when the trial results were discussed at a conference prior to publication, some gave them a more muted reception. Lon Schneider at the University of Southern California commented to Alz Forum that the effect sizes of the outcome measures were too small to be meaningful and that the results did not “demonstrate clinical benefit.”
Around the same time, another set of clinical trials of a different GLP-1 produced a disappointing result in an Alzheimer’s cohort.
The evoke and evoke+ trials were carried out by Novo Nordisk to test its oral semaglutide product against a placebo for at least two years. Semaglutide is the same ingredient in their Ozempic product, but this formulation is taken as a pill rather than being injected.
The conclusion of the 3,800-strong trials was that the GLP-1 “was not efficacious in slowing clinical progression in participants with early Alzheimer’s disease.”
The result was a serious blow to the company's hopes for its drug, and its share prices dropped sharply when the topline results were first announced.
But according to Edison, speaking to the Imperial College news team, the result may simply indicate that an oral GLP-1 – while it may be better for patients using the drug for diabetes management or weight loss – may not be the best at getting to the brain.
“A negative trial result may indicate lack of drug access to the brain, rather than failure of the concept itself.”
Dr Ivan Koychev, a neuropsychiatrist also at Imperial College London, added: “This is a recurring theme in Alzheimer’s disease therapeutics. When pathology is advanced, preventing further biochemical decline is not necessarily enough to restore complex neural networks that have already deteriorated.”
"No trial is wasted"
Alzheimer’s disease is often only diagnosed after years of damage have quietly built up in the brain. It’s also generally a condition that affects older people, with all the neuronal wear and tear that has had a chance to accumulate over a lifetime.
Once that damage has happened, there’s no way to reverse it. The best we can hope for, at present, is slowing down the rate of decline.
One goal of Alzheimer’s researchers is to combine advances in diagnostics with advances in drug therapies, allowing us to detect the disease much sooner and get treatment in place before wear and tear builds up.
The trouble is, no one can seem to agree on what bits of the complex pathology of Alzheimer’s we should be focusing on.
The latest class of drugs that target amyloid-beta, an Alzheimer's-linked protein that forms plaques in the brain, was found by a recent Cochrane review to have "no clinical benefit," despite the fanfare that accompanied some of their approvals. The review sparked fierce debate among scientists.
Edison has suggested that GLP-1 drugs could be valuable in that they seem to target multiple disease mechanisms simultaneously, and so there's a possibility they would slow Alzheimer’s down if used early in the disease process.
One big question that remains is whether these additional effects of GLP-1 drugs can be explained by their impact on diabetes control or their weight loss action.
Obesity is a risk factor for Alzheimer’s disease and many other diseases, and research has yet to tease out whether any positive effect on cognitive decline in people taking GLP-1s is happening independently of weight loss or because of it.
The question of actually getting the drugs into the brain also remains non-trivial. The evoke and evoke+ trials showed that an oral pill may not be the way to go, but that doesn't mean it’s the end of the road for GLP-1s as a whole.
A 2024 review stated that GLP-1s "show clear protective effects" – not just in Alzheimer's but in Parkinson's disease too.
A recent study examined the results of 30 preclinical experiments involving GLP-1s in Alzheimer’s and concluded that there was good reason to continue clinical trials in humans.
“With more than three‑quarters of preclinical studies showing reductions in amyloid‑beta or tau, and early signals emerging from studies on humans, GLP‑1 drugs remain strong candidates for future Alzheimer’s prevention trials,” said lead author Dr Simon Cork at at Anglia Ruskin University, UK, in a statement.
Commenting on the evoke and evoke+ trial results, UK charity Alzheimer’s Society said “Although disappointing for many, no trial is wasted. Every investigation helps us develop better drugs and design better trials in the future.”
“Research is hope and there are currently over 130 Alzheimer’s drugs in clinical trials of which around 30 are in late-stage trials, the final step before they are considered by regulators. There are trials ongoing across the globe that test drugs for dementia.”
