They have taken the celebrity world by storm as a slimming jab and become a vital tool for managing type 2 diabetes. Now drugs such as Ozempic are being researched to look at whether they could help conditions ranging from alcohol misuse to dementia.
Ozempic, a type 2 diabetes medication, and Wegovy, which is licensed for weight loss, contain the drug semaglutide, while a similar drug, liraglutide, is available for both purposes under different brand names.
These medications have become hugely popular, not least because they can help people lose more than 10% of their body weight. Researchers who hope the drugs could bring further benefits are setting up clinical trials.
Dr Christian Hendershot, director of the clinical and translational addiction research programme at the University of North Carolina at Chapel Hill, said: “We know that drugs in this class are remarkably effective for several important health outcomes – many of which can influence longevity and quality of life.
“In some ways there is a sense that some of this might be too good to be true. But I think any potential benefits should be investigated.”
Dr Harshal Deshmukh, a consultant endocrinologist and senior clinical lecturer at the University of Hull, said: “Excessive weight has been identified as a significant risk factor for a range of comorbidities, including fatty liver, various cancers, dementia, and cardiovascular diseases.
“Given these associations, it’s not surprising that numerous clinical trials are currently investigating the potential impact of semaglutide on these health conditions.”
This month the company that produces Wegovy, Novo Nordisk, announced the weight-loss jab can reduce the risk of major cardiovascular events, such as stroke or heart attack, by 20% in people who are overweight or living with obesity.
But scientists say it is not clear if the results are down to weight loss alone, noting it is possible the drug could be having direct effects on blood vessels or the heart.
Experts also hope drugs such as semaglutide could make a difference to polycystic ovary syndrome (PCOS). The disorder, thought to affect an estimated 8-13% of women of reproductive age, can cause irregular periods, hormone imbalances and infertility. It is also linked to insulin resistance and a higher risk of type 2 diabetes.
“Central to the management of PCOS is weight loss,” said Deshmukh, who is running a trial to explore the effect of semaglutide on weight, androgen reduction and quality of life in women with PCOS.
But, Deshmukh noted, there are other potential mechanisms by which the drug may help.
“Notably, the receptors impacted by semaglutide are also expressed within the female reproductive pathway,” he said, adding this includes a system which encompasses the hypothalamus and ovaries, meaning there could be a hormonal pathway at play.
While Deshmukh and others stress rigorous research is needed, they hope semaglutide could help to tackle the spectrum of PCOS symptoms – potentially including infertility by boosting rates of ovulation.
Some trials are even looking at whether these drugs could bring benefits for ageing.
Dr Tiffany Cortes, of the University of Texas, is running one such trial. She said that as people get older they tend to lose lean body mass and gain body fat. Crucially, obesity and insulin resistance feed into syndromes often seen in older adults, such as frailty, loss of muscle mass and strength.
She said the hope was that drugs such as semaglutide could help older people regain physical function, whether because of the direct impact of weight loss or through other mechanisms.
But not every condition for which drugs such as semaglutide are being trialled has links to excess weight.
Hendershot is among those planning to explore the impact of these drugs – known as GLP-1 analogues – in the area of addiction.
Hendershot says the drugs mimic GLP-1, a hormone that is produced naturally in the brain and the gut in response to food ingestion. They promote feelings of fullness and, it seems, dampen the reward associated not only with food but also drugs.
The idea came about after people given GLP-1 analogues for diabetes reported reductions in their alcohol consumption. Hendershot said animal models suggested the medications could affect drug-seeking and consumption.
“The findings have been consistent, especially for alcohol,” Hendershot said.
Even dementia researchers are turning to drugs such as semaglutide, after studies suggested people who took GLP-1 analogues for type 2 diabetes had a reduced incidence of such conditions.
Dr Paul Yates, a consultant geriatrician and deputy director of aged care research at Austin Health, Australia, is among those working in the area. He said GLP-1 and its analogues appeared to have beneficial effects in the brain.
“Our current study is aiming to slow [dementia] down, as it is recruiting people who already have symptoms,” he said.
While GLP-1 analogues such as semaglutide might sound suspiciously like a potential panacea, experts say the situation has some logic.
“We should always be sceptical but this might be different,” said Dr Kyle Simmons of Oklahoma State University, who is also looking at whether semaglutide could help people with alcohol use disorder. “And the reason why is because it gets at biological pathways that are so central to our survival.”
But researchers admit there are concerns and unknowns.
Many of the clinical trials are in their early stages – meaning some hoped for applications could fall by the wayside over the coming years.
It is also unclear whether the drugs would benefit all people with a certain condition, and whether they can safely be used in people who are not overweight or living with obesity.
Another concern is that the drugs could quash reward signalling generally in the brain.
“You do worry, for example, in people maybe who have a history of depression, who were remitted, if the medication could be enough to tip them back into a relapse,” said Simmons.
Then there is the problem of accessibility for researchers and patients, given shortages and expense of the medications.
And even if trials are successful, there is the matter of licensing, while there are also questions about how long people would need to take the GLP-1 analogues. Experts have previously warned that when weight-loss patients stop the medications their weight often bounces back.
Yet despite a dose of caution, researchers such as Simmons seem upbeat, excited even.
“These drugs are already changing the world, we just don’t know whether they will change how we treat addiction,” he said.
