How Ozempic became the new wonder drug

ozempic
One of the UK's leading cardiologists recently revealed that weekly injections of semaglutide could reduce risk of cardiovascular events by 20 per cent

Earlier this year, I was on a conference call regarding the future of nutrition, when one of the speakers jokingly suggested that GLP-1 drugs – the class of diabetes and weight loss medications which include Ozempic, Wegovy, and now newer alternatives such as Mounjaro – should be “put in the water supply”.

While made in jest, and there are no actual plans to make weight loss drugs the new fluoride, research is increasingly showing that apparent benefits of these medications stretch far beyond helping people shed excess pounds.

Earlier this week, Prof John Deanfield, one of the UK’s leading cardiologists, revealed that weekly injections of semaglutide, the medication in Ozempic and Wegovy, could reduce risk of cardiovascular events such as heart attack and stroke by 20 per cent, suggesting they could be used in a similar manner to statins.

Prof Denfield was presenting the latest results from a clinical trial called Select at the European Congress on Obesity. Following more than 17,000 people with a body mass index (BMI) of at least 27, over the course of three years, the aim was to assess whether semaglutide could have a protective effect in individuals with an existing history of cardiovascular problems.

Dr Riyaz Somani, a consultant cardiologist at University Hospitals of Leicester NHS Trust, described the results as ‘truly remarkable”.

“The implications are huge and are likely to lead to changes in current practice,” he says.

So how has semaglutide become established as a generation-defining medicine? 

Obesity and heart disease

Outside of industry insiders, few people had heard of semaglutide, a drug manufactured by the Danish pharma company Novo Nordisk, until the publication of an astonishing clinical trial in 2021. It demonstrated that people taking a weekly 2.4mg injection of the drug could shed up to 20 per cent of their starting weight over the course of 15 months.

At the time, Prof John Wilding, a cardiovascular and metabolic medicine expert at the University of Liverpool who ran the trial, described it as a potentially landmark moment in the fight against rising rates of chronic obesity.

“Educating people to make healthier choices with their diets is a really good idea,” he says. “But this isn’t going to help the average person who comes to my clinic, who weighs maybe 125-130 kilograms, perhaps already has diabetes, and is waiting for a knee replacement that the surgeon’s reluctant to do because the chances of complications are so great due to their weight. With these people, dieting has an almost 100 per cent failure rate because the body responds to losing weight by reducing all the hormones that make you feel full, so you feel hungry all the time.”

Because semaglutide mimics a natural occurring gut hormone called GLP-1, which is part of the brain’s appetite control system, it actively reduces hunger and cravings, making dieting much more manageable.

Now it appears that the same weekly dose of semaglutide can also offer long-term benefits for the heart and blood vessels. However as Dr Martin Whyte, an associate professor of metabolic medicine at the University of Surrey, points out, the intriguing aspect is that this does not appear to purely be a surplus benefit of weight loss.

“What was surprising was that the same reduction in cardiovascular events was seen in those who lost less than 5 per cent body weight, and those who lost more weight,” says Dr Whyte. “In other words, something else is in play.

Some of the additional data collected as part of the trial may help to indi

cate why. It seems that a weekly dose of semaglutide can directly reduce blood pressure, reduce blood fat levels and also lower levels of C-reactive protein, a marker for inflammation. This corresponds to previous research studies in animals which have suggested that drugs mimicking the GLP-1 hormone can reduce inflammation, reduce risk of blood clots, and improve heart function.

In the wake of these findings, Prof Deanfield is convinced that the NHS should consider implementing a mass rollout of Ozempic or Wegovy to anyone with a BMI over 27, in a similar manner to statins. However, others feel that there are still many questions to be assessed, not least whether the NHS could actually afford this.

“Before deciding on a wider use of the drug, we would need a cost-analysis so that we know whether the NHS would get good value for money with this treatment,” says Richard Holt, a professor of diabetes and endocrinology at the University of Southampton. “We had a lot of the same arguments about cost effectiveness when statins first came out, but they are a lot cheaper. Another big difference is that semaglutide is given by injection, not orally as happens for statins, which will put some people off using it.”

Diabetes

The original application of semaglutide was Type 2 diabetes, and the Ozempic formulation is still marketed as a diabetes treatment (the manufacturer says the drug is only indicated for the treatment of adults with insufficiently controlled Type 2 diabetes mellitus and that a weight-management medication would be considered ‘off-label’). Prof Holt explains that the drug is known to improve blood sugar control by interacting with two other hormones – insulin and glucagon.

Various clinical trials of semaglutide in Type 2 diabetics have found that between 67 and 80 per cent of participants reached their target blood sugar levels.

“Semaglutide increases the amount of insulin produced by the pancreas in response to eating, which helps to lower blood sugar after consuming food,” says Prof Holt. “At the same time it reduces the amount of glucagon being produced, a hormone which works against insulin. Semaglutide also slows gastric emptying and so the rate of food absorption from the gut is slowed.”

Addictions

Just as semaglutide decreases cravings for food, an increasing mass of evidence over the past year has suggested that it can have a potent impact when it comes to breaking all kinds of substance addictions from alcohol to cannabis. Animal studies have also suggested that it can decrease desire for nicotine, suggesting it may offer a new way of curbing smoking or vaping addictions, while some researchers in the United States are even trialling liraglutide, another drug which mimics the GLP-1 hormone in patients with opioid addictions.

W Kyle Simmons, a professor at Oklahoma State University, is now leading a clinical trial to assess whether semaglutide can be used as a novel treatment for alcohol use disorder.

He explains that one of the major theories is that semaglutide binds to a part of the brain called the hypothalamus which is connected to a brain network known as the mesolimbic dopamine pathway, which is stimulated by alcohol and all kinds of addictive substances.

“Semaglutide binds to receptors in the brain involved in dopamine signalling,” says Prof Simmons. “These regions play a significant role in making us want and enjoy things that make us feel good.”

Animal studies suggest that semaglutide can actively reduce the amount of dopamine released in these brain regions, thus helping to curb the cravings.

Dementia

Semaglutide is even being assessed in various trials to examine whether it can slow cognitive decline in older adults who are thought to be at risk of dementia. Many people experience mixed dementias which are partially driven by damage to the heart and the blood vessels supplying the brain, but as well as semaglutide’s restorative effect on these systems, researchers are also interested to see whether it can dampen brain inflammation and the accumulation of toxic tau proteins, two of the driving forces behind Alzheimer’s disease.

“It might stop or slow some of the deterioration in the nerve cells that occurs in Alzheimer’s disease,” says Dr Tomas Welsh, the medical director of the Research Institute for the Care of Older People, who is involved in some of these trials.

Risks

While researchers across all various medical specialties are extremely excited about semaglutide’s potential to treat all kinds of diseases, it may not be suitable for every patient. Prof Holt points out that in the Select trial, one in every 12 participants was forced to quit the drug, mainly due to gastrointestinal side effects which can range from heartburn to bloating, and recurrent stomach pain or discomfort.

Another challenge, particularly for middle-aged and older individuals is that people taking semaglutide do not only shed fat mass but a significant amount of muscle. This can make people more vulnerable to frailty, falls and fractures and can greatly impact mobility.

Dr Whyte also cautions that we still know relatively little about the long-term health consequences of semaglutide and what may happen if people end up taking it indefinitely, as may be required to lower their risk of cardiovascular disease.

“The long-term effects are not known with semaglutide as it has been relatively recently introduced,” he says.

Finally, others are concerned about the prospect of creating a society which is over reliant on medication as a way of tackling a set of diseases which are predominantly linked to poor lifestyle habits. Prof Keith Godfrey, the nutrition lead at the NIHR Southampton Biomedical Research Centre, explains that the NHS money spent on semaglutide could result in other resources becoming underfunded.

“Building structures that primarily depend on medical treatments to mitigate obesity [and related diseases] carries a significant risk of unintended consequences,” says Prof Godfrey. “It is often the case that rare, unforeseen risks only emerge after a drug is rolled out for widespread general population use. And preventative public health measures, particularly those that look to prevent obesity in children, must never be de-prioritised.”

But while these misgivings must be taken into consideration, if clinical trials continue to generate positive results, semaglutide could well become one of the most far-reaching and revolutionary drugs in history.

“The Select study results are good news because it highlighted semaglutide’s effectiveness as a weight-reducing agent as well as suggesting that it actively lowers cardiovascular disease risk through other mechanisms,” says Prof Holt. “This is all very important because obesity is also a risk factor for other conditions such as cancer, arthritis and liver disease.”

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