It is a drug that has dominated headlines, first as a medication for type 2 diabetes, then as a weight-loss aid. Now it seems semaglutide – often called by its brand names Ozempic or Wegovy – could bring benefits in myriad areas of healthcare, from addiction to dementia.
Diabetes
Semaglutide, which can be taken as a tablet or via injection, mimics a hormone produced in the body called GLP-1 – a substance that is released in the gut when we eat.
GLP-1, and hence also semaglutide, slows the rate at which food is digested in the stomach, and acts on the brain to reduce appetite. Crucially, it also triggers an increase in the production of insulin – a hormone that plays an important role in regulating blood sugar levels.
Myriad studies have shown regular dosing with semaglutide results in significant improvements in blood sugar control in people with type 2 diabetes – although some trials have been funded by the maker of the drug, Novo Nordisk.
As a result, drugs such as semaglutide are available on the NHS for people with type 2 diabetes and are considered a valuable tool.
Weight loss
A key finding from studies looking at semaglutide for type 2 diabetes was that the drug is associated with a reduction in body weight. As a result, semaglutide has found a new market as a slimming aid in people without type 2 diabetes, nicknamed the “skinny jab”.
Research published in the New England Journal of Medicine, involving 1,961 overweight obese adults without type 2 diabetes, found that while those given a placebo in addition to lifestyle interventions lost an average of 2.6kg over the course of the 68-week study, those given a weekly injection with semaglutide alongside lifestyle interventions lost 15.3kg on average.
Experts say drugs such as semaglutide are an important tool for managing the obesity crisis but many also warn that such drugs do not tackle the root cause of the issue.
At present GLP-1 mimics, including semaglutide, are available for some groups on the NHS, although prescriptions can only be given for a maximum of two years because of a lack of long-term data.
However, results from a trial known as the Select study have shown that continued treatment for four years is not only safe but associated with sustained weight loss.
“It is very encouraging that continued treatment for four years or so is effective in helping people to lose weight at a clinically significant level of 10% on average,” said Tricia Tan, professor of metabolic medicine and endocrinology at Imperial College London.
“Previously, the only evidenced and effective long-term treatment for obesity was weight-loss surgery where we have evidence that surgery is capable of giving long-term weight loss for 20 years or so. This trial helps to support the idea that semaglutide is effective at least in the medium-term.”
But semaglutide is not without side-effects, with some quitting the study because they felt sick or experienced diarrhoea.
Heart attacks
The Select study previously suggested a weekly dose of semaglutide could reduce the risk of heart attack, stroke and death from cardiovascular causes in overweight or obese adults with pre-existing cardiovascular disease by about 20%.
However analysis of the research – yet to be published – has revealed the proportional reduction in such events holds regardless of participants’ starting weight.
The results have led some experts to suggest semaglutide should be routinely prescribed to treat cardiovascular illnesses. However others say there are still unknowns –including the mechanism involved – that may limit such applications.
Dementia
Studies have suggested the rate of dementia is lower in people with type 2 diabetes who take GLP analogues, such as semaglutide, compared with those given a placebo.
As a result, researchers have teamed up with manufacturers to run trials exploring whether the drug could help people with early Alzheimer’s disease.
“In our study we are giving it to people who do not have dementia but are at risk through having high levels of the Alzheimer’s disease protein amyloid in-brain,” said Dr Ivan Koychev of the University of Oxford.
When it comes to dementia, there are several mooted mechanisms by which semaglutide might being benefits, from reducing inflammation in the brain, to reducing the accumulation of proteins associated with Alzheimer’s disease.
“This class of drugs is [also] known to reduce risk of vascular events and so the effect on dementia may be through reducing the incidence of major strokes or reducing the likelihood of smaller blood vessel scarring,” added Koychev.
While Koychev is optimistic, it is worth noting many highly promising dementia drugs have fallen by the wayside as trials progressed.
Addiction
This is a promising area for semaglutide given the drug appears to not only dampen the reward system associated with food but drugs, too.
Indeed research has previously suggested GLP-1 analogues are associated with reduced alcohol consumption and a greater chance of smoking abstinence. Studies in mice and rats have also suggested the medications change addictive behaviours, reducing drug-seeking and consumption.
However large scale, robust studies in humans are needed, while it is unclear if such drugs dampen reward signalling generally in the brain – raising concerns around their use in people with depression.
Polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is thought to affect 8-13% of women of reproductive age, and can cause irregular periods, hormone imbalances and infertility.
While it is thought semaglutide might help people with PCOS because of its effects on weight loss, experts have suggested other mechanisms could also be at play.
Trials are now under way to explore whether semaglutide could help boost rates of ovulation among those with PCOS – an outcome that could also improve fertility – as well as its impact on levels of hormones, including testosterone.
Cancer
While there have been concerns that GLP-1 mimics might raise the risk of thyroid and pancreatic cancers, recent research has cast doubt on these worries.
Studies have even suggested such drugs could help to reduce the risk of certain cancers, with research published last year suggesting they are associated with reduced risk of colorectal cancer in people with type 2 diabetes both with and without extra body weight.
With more pronounced effects found in overweight and obese patients, the authors say the results could, at least in part, be down to such drugs helping people to lose weight.
Prof Simon Cork of Anglia Ruskin University said the theory makes sense.
“Obesity is known to increase the risk of at least 13 different types of cancer so reducing body weight would almost certainly reduce ones risk for those particular cancers,” he said.
