Wegovy, Ozempic, weight loss - and the future of obesity

"They say: 'For they first time in my life I know what it's like to feel full - that part of my brain has been switched on'," said Barbara McGowan, a professor of endocrinology and diabetes at King's College London.

She was speaking on Wednesday during a media briefing organised to give an overview of what we know so far about these drugs, and where we may be heading.

It came just days after the UK Government issued an national patient safety alert to healthcare providers instructing them to stop "off-label" prescribing of the medications for slimming, warning that the practice was putting the lives of diabetes patients in danger.

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In the UK, there are limited supplies and strict instructions on how and when the drugs can be used on the NHS, but in some cases private clinics and online suppliers have been selling them as an appetite suppressant purely to aid weight loss.

There are three main brands of GLP-1 currently on the market: Wegovy (2.5mg semaglutide); Ozempic (semaglutide doses ranging from 0.25 to 1mg), and Saxenda (liraglutide).

They are all administered by injection and are all manufactured by the same Danish company - Novo Nordisk.

Ozempic has become known as a celebrity weight-loss drug after a number of high-profile people including Jeremy Clarkson and Elon Musk revealed they were using it (Image: Getty)

Global demand is so high that Novo is in the process of constructing new factories to ramp up production, but stocks are not expected to stabilise until mid-2024.

Even with the strict criteria currently used by the NHS - very high BMIs, Type 2 diabetes or high blood sugar, access to weight-loss management programmes, additional complications such as high blood pressure or cholesterol - it is still estimated that 10 million adults could be eligible for the medicines.

However, there is a growing sense among scientists that this will expand if - as expected - evidence accumulates on their health gains and safety profile.

This may include prescribing them as a preventative intervention among younger adults - even teenagers - who are at risk of obesity and diabetes. 

This is a potentially significant health intervention given that developing diabetes at a very young age is associated with a 15-20 year loss of life expectancy compared to virtually none for someone who develops the disease aged 80.

Carel Le Roux, a professor of metabolic medicine at Ulster University, stressed that we "don't have the evidence to support that at the moment", but may do in future.

He added: "That's exactly what we did with statins: we started using them in people at risk of heart attacks rather than people who had had a previous heart attack.

"But that evidence is still awaited, and we will wait some time for it I would suggest."

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For Prof Le Roux, existing evidence is already exciting.

Randomised control trials comparing outcomes in patients on semaglutide compared to a placebo have found significant benefits.

Over a 68 week period, rates of metabolic syndrome - the umbrella term for a combination of diabetes, high blood pressure, and obesity - fell from 53.3% in both groups to 24.6% among those on semaglutide compared to 48% for those on the placebo.

Levels of C-reactive proteins - a blood biomarker for inflammation - also dropped more steeply among those on semaglutide, by 53%, versus 15% for those on the placebo.

"Here you have this idea that you can take patients who are at risk of disease, who have a syndrome, and we can turn the clock back, and make them healthier," said Prof Le Roux.

There is optimism that the drugs could reduce the overall impact of obesity-related cardiovascular diseases on the population (Image: Getty)

Similarly, evidence from Glasgow researchers shows significant reductions in stokes, heart attacks, hospital admissions for heart failure, and all-cause mortality among diabetes patients on GLP-1 drugs.

There is also an expectation that the current two-year cut-off for NHS prescriptions of GLP-1 drugs will be overturned in favour of long-term - possibly lifetime use - as an increase in competition from rival companies drives down price.

At present, the price increases steeply after two years, tipping the cost-effectiveness equation out of balance.

New data released yesterday by pharmaceutical giant, Eli Lilly, indicates that patients taking its GLP-1 drug Mounjaro (tirzepatide) lost 26% of their bodyweight - but that this relapsed when they stopped. 

A second driver could be data emerging from a series of long-term clinical trials which are due to report in the coming months.

One study, exploring the benefits of high-dose semaglutide in 500 people living with heart failure, is due to report its findings at the European Society of Cardiology (ESC) conference in Amsterdam in August.

The most anticipated, however, is the SELECT trial, which will present its findings in November.

This is a six-year study tracking 17,500 non-diabetics over the age of 45, with a prior heart attack, stroke or peripheral arterial disease, and a BMI over 27 to determine the safety and effectiveness of taking a regular high dose of semaglutide long-term.

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The drugs, which mimic a human gut hormone, help people feel full for longer - suppressing their appetite (Image: PA)

Work is also ongoing to combine existing GLP-1 medicines with other gut hormones to create even more potent drugs capable of delivering weight-loss on a par with bariatric surgery. 

Naveed Sattar, a professor of metabolic medicine at Glasgow University, said: "Clearly we would love the food environment and the physical activity environment to improve to such an extent that we could prevent obesity and all the complications that come from it - we still really want that to happen.

"But do I foresee that that is going to change substantially and sufficiently to slow the obesity gains? I'm not sure.

"We can't medicate our way out of ill health - but if these drugs give rise to a nation which is healthier and happier and more productive, and we have less health cost, less multi-morbidity, that can only be good.

"We're optimistic, but let's look at the benefits versus the safety and let's see how these trials work out. 

"With more data we get a regression to the truth."