Why Ozempic could be the answer to ageing (and it’s not about weight loss)

In the wake of early evidence supporting the long-term health benefits of GLP-1 based medications to potentially reduce the risk of cancer, dementia and more – could they also be potent anti-ageing tools of the future?

For future generations, it’s quite plausible that their most important 50th birthday present will be an Ozempic prescription from their GP, designed to slow down the ageing process and prolong their years of good health.

That’s the provocative suggestion of Gaetano Santulli, Associate Professor at the Albert Einstein College of Medicine in New York, one of the world’s foremost hubs of ageing research. He says evidence is increasingly pointing to a role for drugs which mimic gut hormones like GLP-1 as potent anti-ageing tools of the future.

“The concept of using gut hormones to delay or prevent aging-related decline in healthy midlifers is biologically sound and increasingly feasible,” Santulli told The i Paper.

His comments arrive in the wake of yet another remarkable flurry of evidence supporting the long-term health benefits of GLP-1 based medications such as Ozempic, Wegovy and Mounjaro.

Gaetano Santulli is the Associate Professor at one of the world’s foremost hubs of ageing research

At the European Congress on Obesity earlier this month, experts unveiled studies demonstrating that the drugs elicit powerful anti-cancer effects – an effect that is independent of weight loss. Others showed GLP-1 drugs halve deaths from heart attacks, and can prevent recurrence of atrial fibrillation, a chronic condition characterised by an irregular heartbeat which is one of the common causes of strokes. Elsewhere, scientists have found taking a weight-loss drug can slow cognitive decline and reduce mental-health problems such as anxiety.

Such findings beg the question: could these drugs one day be taken by slim people, too, to help them live a longer life without disease?

When GLP-1 drugs first emerged onto the scene five years ago, it was thought they would reduce chronic illnesses through their ability to tame appetite, thus eliciting dramatic reductions in weight and body fat in a matter of months or years. With obesity being an underlying cause of many different chronic illnesses, this has long been assumed to be the primary reason why the drugs seem to show effectiveness in conditions ranging from severe fatty liver disease to sleep disturbances.

However, as Santulli explained, the growing excitement stems from emerging data both collected in clinical trials and in the lab, demonstrating that their positive impact on the body stretches far beyond weight loss. In fact, he says, it’s becoming increasingly clear that GLP-1 drugs can modulate some of the most fundamental biological processes behind ageing.

For one thing, they appear to boost the immune system, enhancing its ability to clear cancer cells before they develop into tumours, while they also dampen down the chronic inflammation which progresses with age. This is thought to be one of the reasons why people with osteoarthritis in their knee joints have reported reduced pain and improved mobility while taking the drugs.

“This is an emerging concept,” says Santulli. “Observations suggest that GLP-1 is much more than a satiety hormone. These drugs reduce systemic inflammation and modify innate immunity. GLP-1 protects against age-related stiffening of blood vessels, alters energy metabolism, and also may tune up systems which protect against age-related damage, making our cells more resilient, in a similar way to exercise.”

Gut hormones and the link to longevity

As one of a small collective of male and female scientists who played a critical role in the discovery of GLP-1 and its many roles throughout the body in the 1980s, Jens Juul Holst is one of ‘the parents of Ozempic.’ As well as working on the basic science, Holst helped alert Danish pharmaceutical company Novo Nordisk – who would ultimately develop Wegovy and Ozempic – to GLP-1’s effects on blood sugar and appetite, but 40 years ago, he had little idea that his work would ultimately lead to some of the fastest selling drugs of all time.

What he did know, even in those early days, was that there seemed to be a connection between this gut hormone and longevity, with people who received bariatric surgery consistently living longer than those who receive standard obesity care.

“We know from the hundreds of thousands of individuals who have received gastric bypass operations that they live longer,” Holst, still an active researcher at the University of Copenhagen at the age of 79, told The i Paper. “The data is very consistent. Now, how do these operations work? They release GLP-1 and another gut hormone called PYY.”

With this in mind, Holst is particularly intrigued by a new idea proposed by Santulli – giving GLP-1 drugs to over 65s, particularly those already in worsening health – perhaps highlighted by blood tests which indicate elevated levels of inflammatory proteins or signs that they are becoming frail and more vulnerable to falls – and seeing whether they can radically boost their health.

Of course, giving appetite-suppressing drugs to older people comes with risks. This age group is already vulnerable to a condition known as ‘anorexia of ageing,’ characterised by diminished appetite and malnutrition. However Santulli believes it could be solved through two means: giving them additional appetite boosting medicines, and treating these people with lower or ‘microdoses’ of GLP-1.

Older generations are vulnerable to a condition known as ‘anorexia of ageing’ (Photo: Alex Tihonov)

“Anorexia would be a real concern, but potential solutions could include lower doses of GLP-1s which still provide the anti-inflammatory benefits and act on ageing pathways without affecting satiety centres in the brain,” he suggests. “And co-administering known appetite stabiliser drugs like anamorelin. You could also proactively monitor their muscle mass and dietary intake to make sure that wasn’t changing.”

It’s a bold plan, and if such a study were to demonstrate positive outcomes, Santulli feels it could potentially pave the way for wider access to GLP-1s, possibly enabling many non-obese individuals in their 40s, 50s and 60s, to reap the wider health benefits.

But for this to become reality, there are still a few challenges which need to be overcome.

A longer life – but a less pleasurable one?

For David D’Alessio, an endocrinology and metabolism professor at Duke University, the single biggest barrier to the concept of making GLP-1 drugs available to midlifers on a mass scale, is one of cost. “In the US, they cost $1000-1500 per month,” he says. “Multiply that times the number of people who don’t want to get old and you get something approaching infinity.”

Two things could change that, the first being the steady expiry of the patents which give drugmakers their monopoly over how these drugs are priced, something which has already begun to take place. Last year, Novo Nordisk’s patent for liraglutide – an earlier GLP-1 drug marketed as Saxenda – expired, and between 2026 and 2033, the company’s various patents over Ozempic and Wegovy and those held by American pharma giant Eli Lilly who make Mounjaro, will end.

This will then allow competitors to step in and make generic forms of these medications, driving the costs down. “Patent expiration is critical for the potential of these drugs to actually have a broad impact,” says D’Alessio.

Secondly, while GLP-1 drugs are currently administered as an injection, which is both more expensive to manufacture and less pleasant for users, companies have begun to crack the riddle of producing them as pills. “That has been very, very difficult, but Eli Lilly has produced one, Orforglipron, which is looking good,” says Holst. “It will be much easier to produce, and eventually cheaper.”

There’s also the question of side effects, both the acute nausea and gastrointestinal issues which a certain number of people experience when taking Wegovy or Mounjaro for obesity, and also the loss of pleasure from eating and drinking, which seems to make GLP-1 drugs highly effective at combating addictions ranging from alcohol to opioids.

Holst says that this even raises an important philosophical question – would people actually want to live longer, if the trade-off was taking a drug which limited some of the enjoyment of life?

“The pharmaceutical companies don’t talk a lot about this,” he says. “But it’s quite well established that the drugs have this effect on reward, and that means it’s not so fun to be on them, especially if you enjoy food, alcohol, all the pleasures of life. So that’s a key challenge – if you just gave everyone a GLP-1 drug, they might just get fed up.”

But as with Santulli’s proposed study in the elderly – microdosing might provide an answer.

Is microdosing the answer?

Given the high costs of GLP-1 drugs, an increasing number of reports have emerged from the US, describing people purchasing vials of Wegovy and Mounjaro and deliberately administering it to themselves in tailored doses, far smaller than the recommended levels.

As well as preserving their supply and saving money, this kind of microdosing has been found to be an effective way of avoiding ongoing side effects, especially for people who have already reached their desired weight goal and simply want to maintain their weight over a longer period of time.

Holst has been intrigued by this development and says that microdosing should now be studied more widely in clinical trials. It may also represent a pathway to broadening access to GLP-1s without excessively dampening pleasure signals in the brain.

For now, he’s doesn’t feel there’s sufficient evidence for these drugs to be used as preventative tools in people who are already in excellent health, but he does believe that they will play an increasing role when it comes to younger people, who are not obese, but are managing autoimmune diseases like type 1 diabetes or have some kind of metabolic syndrome, for example insulin resistance or elevated blood pressure.

“In many countries, there’s something like a quarter of the adult population with metabolic syndrome which gives them a greatly increased risk of cardiovascular disease and premature death,” he says. “It’s a huge number of people, and we know that GLP-1 drugs can do something about that. So I feel there is a fantastic opportunity – and almost an obligation – for governments to use these medications to reduce their risk.”

Going forwards, Holst predicts that eventually we could reach a situation where people can go to their GP and have a blood test, and if they’re showing signs of poor metabolic health, they can be prescribed a GLP-1 medication to help normalise those symptoms before they develop into something more serious.
“You’d get a blood sample taken, look at your blood lipids, your cholesterol levels, blood pressure and things like that,” he says. “It’s going to be like statins.”

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