Does Ozempic also hold the secret to a cure for depression and dementia?

By now we’re all aware of how effective the drugs Ozempic and Wegovy are for weight loss. Whether it is an A-lister, an influencer or just someone in our inner circle, hardly a day goes by without some kind of chatter around someone who has suddenly dropped three stone and whether they are “on the pen” (shorthand for the weekly injections of the drugs).

And now a study by Health Innovation Manchester and Lilly will examine whether being put on the drugs will reduce worklessness and the impact on NHS service use, and will take place in Greater Manchester.

The health secretary, Wes Streeting, said: “Our widening waistbands are also placing significant burden on our health service, costing the NHS £11bn a year – even more than smoking. And it’s holding back our economy.

“Illness caused by obesity causes people to take an extra four sick days a year on average, while many others are forced out of work altogether.”

However, while the drugs were originally created to treat type 2 diabetes and obesity, what’s less well known and currently being investigated, is the drugs’ potential impact on a whole raft of other serious health conditions, including dementia, depression heart attacks, stroke, liver failure, polycystic ovary syndrome (PCOS), Alzheimer’s and even addiction.

Already, the drugs’ maker, Danish pharma company Novo Nordisk, is undertaking trials with dementia patients, with full results expected in 2025.

A study from Oxford University recently published in The Lancet earlier this year examined over 100 million US patient records and found that those prescribed Ozempic had lower rates of cognitive decline and also, experienced lower nicotine cravings – although all patients in the study had diabetes and researchers warn that further trials are needed.

Early signs, however, are hugely encouraging, mostly down to the fact that semaglutide, the drug that Ozempic and Wegovy are brand names for, works, by activating the GLP-1 receptors in the brain. And these GLP-1 receptors have been found to calm bodily inflammation – a key factor in triggering or exacerbating serious disease.

When the drug is injected, insulin is released into the body, our blood sugar level is lowered, and “fullness” hormones are triggered, which is how it controls appetite. But it seems semaglutide does a few other things as well. 

Dr Steven Allder, consultant neurologist at Re:Cognition Health says: “Semaglutide might impact the brain through several mechanisms. By improving blood sugar control, semaglutide can reduce the risk of diabetes-related cognitive decline. High blood sugar levels can damage blood vessels and neurons, too, contributing to dementia.”

He also points out that “chronic inflammation is linked to neurodegenerative diseases. Semaglutide’s anti-inflammatory properties may help reduce brain inflammation, and directly protect neurons by improving cellular repair mechanisms and reducing oxidative stress.” (Chemical chain reactions in the body, triggered by “free radicals” – toxic molecules caused by metabolism or pollution.)

Of the latest study, he adds, “I believe it’s a plausible finding that could increase interest in reducing inflammation to prevent long-term conditions.”

Researchers are now investigating the direct effects of semaglutide on the brain and the list of other conditions it could be used to treat in the future is impressive. While Dr Adam Moreton, consultant older adult psychiatrist at Pall Mall Medical, says as the medications are still relatively new, and “will take a while for any changes to be noticed via routine hospital clinics”, the conditions under review mean that if the results are as impressive as they initially look, it truly could be the holy grail of health. 

“The Oxford study indicates that Ozempic and Wegovy are associated with a lower risk of cognitive problems in patients with type 2 diabetes,” says Dr Moreton. 

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“The benefits may arise from reducing the risk factors which increase the chance of developing dementia.” In Alzheimer’s, he explains, brain cells are damaged by proteins called tau and amyloid, causing areas of the brain to die. “By contrast, vascular dementia means blood vessels narrow and become blocked, in a similar way to stroke.”

Medications are available to “mask” symptoms of Azheimer’s, Dr Moreton explains, “but they don’t actually stop the disease from progressing. The newer medications, which have been in the news recently, do something different – they reduce levels of amyloid in the brain early in the dementia process.” However, there is no equivalent medication for vascular dementia. 

“That might be where semaglutide medications come in,” he says.

Inflammation reduction in the brain may also support semaglutide’s use in cognitive diseases, as GLP-1s are able to control immune function in the brain, blocking protein build-up as well as lowering inflammation in the neural pathways. 

One trial last year found that Alzheimer’s patients treated with liraglutide (a similar drug) had a reduction in cell shrinkage and less cognitive decline than those not on the medication. Dr Ivan Koychev who led the Oxford study, says, “This class of drugs is known to reduce risk of vascular events and so the effect on dementia may be through reducing the likelihood of smaller blood vessel scarring.”

The early signs are that semaglutide could be helpful in both Alzheimer’s and vascular dementia – and its uses may become even clearer when the Novo Nordisk trial concludes next year.

Earlier this year, an analysis of four million patients by Epic, a medical records company, found that the majority of GLP-1 medications led to a reduced likelihood of depression and anxiety. Non-diabetic patients on semaglutide were significantly 37 per cent less likely to be depressed, and 31 per cent less likely to be diagnosed with anxiety. 

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A meta-analysis also suggested a reduction in depression among patients with diabetes who were taking the medication. Researchers pointed out that the mental health benefits might be due to weight loss – there’s an established connection between obesity and depression, as well as anxiety. But now scientists are looking deeper into the initial findings. 

Assistant professor Rodrigo Mansur from the University of Toronto who has researched the effects of semaglutide, believes the presence of GLP-1 receptors in areas of the brain responsible for cognitive function and emotional control certainly plays a significant role in reducing depression and anxiety beyond a “mind trick”.

His 2017 study found, “on average, depressive symptoms improved by 30 per cent – regardless of weight loss”. Further MRI brain scans of participants found that the brain areas related to planning, organisation and emotional processing noticeably increased in volume within just a few weeks.

The anti-inflammatory effect is what’s currently thought to reduce heart attack risk. A recent, large select study from UCL’s Institute of Cardiovascular Disease found “cardiovascular advantage” in non-diabetics taking semaglutide.

Participating adults who had previously suffered a heart attack, stroke or arterial disease, who were overweight or obese but not diabetic and took semaglutide for over three years had a 20 per cent lower risk of heart attack, stroke, or death due to cardiovascular disease.

Study leader Professor John Deanfield said: “These findings have important clinical implications. Around half of the patients that I see in my cardiovascular practice have levels of weight equivalent to those in the select trial and are likely to derive benefit from taking semaglutide.”

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The effect on cardiovascular health was independent of any weight loss.

“These alternative mechanisms may include positive impacts on blood sugar, blood pressure, or inflammation,” says Professor Deanfield, “as well as direct effects on the heart muscle and blood vessels, or a combination.”

Other studies have indicated preventative effects against stroke and epilepsy, as seemingly, the drug’s protective effects relating to dementia may also have an impact on neuro-inflammatory diseases, such as Parkinson’s and Alzheimer’s.

Thanks to their ability to target inflammation, the possible applications of the drugs are wide, and now, even addiction is coming under the semaglutide spotlight. Earlier this year, researchers from Penn State Neuroscience Institute presented the first trial results using the drug to treat addiction to opioids.

Though a small study (just 20 patients), the results were impressive, with those on the drug experiencing a 40 per cent reduction in cravings. When activated, GLP-1s appear to target the brain areas connected to reward and craving, and reduce activity in those regions. The pleasure of a “hit” is reduced, and the pain of withdrawal is lessened, too.

Meanwhile, UTHealth Houston’s studies with mice indicated that Ozempic and Wegovy (semaglutide), and other similar drugs Victoza (liraglutide), and Byetta (exenatide), reduced “nicotine-seeking behaviours”, too. “At least one of the mechanisms of how these drugs reduce alcohol drinking is by reducing the rewarding effects of alcohol,” said a study leader.

The belief is that it may work for nicotine in a similar way. Addictive substances can increase dopamine production, so one way in which the drugs work may be by reducing that flow.

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It is also why semaglutide may be useful in treating eating disorders, after a University of Oklahoma study found it offered better results than the current (US-based) medication used to treat binge eating disorders.

Researchers think it may be able to help patients with anorexia and bulimia too, although more research into the effects is needed. It seems GLP-1 can help to control stress, mood, cognitive function and reward, and the effects of any drug or behaviours which normally trigger these areas of the brain may be alleviated.

Future studies into the use of Ozempic and Wegovy will rely on academic funding as Ozempic’s manufacturers Novo Nordisk have no current plans to study the other applications for the drugs. They are, however, looking into clinical trials for alcohol-related liver disease, with a view to discovering whether semaglutide can improve liver health and fibrosis (scarring).

Excitingly, there is even some early research being done into looking into the effect of the drugs on certain cancers that may be triggered by inflammation.

A study in the JAMA Network Open medical journal looked at the records of 1.6 million patients with no prior history of obesity-related cancer, and found those treated with GLP-1 medication had a “significant risk reduction” in 10 specific cancers, including gallbladder and kidney.

As of yet branded medications such as Ozempic and Wegovy are only prescribed for type 2 diabetes and weight loss, and must be prescribed by a doctor.

If further studies do reveal these drugs to have a significant impact on some of the world’s deadliest and most debilitating diseases, it may yet transpire that semaglutide really is the wonder drug we have been waiting for.