The study that says semaglutide can do much more than help you lose weight

Good morning. If you hear brand names like Ozempic and Wegovy and think of suddenly gaunt A-listers posing on the red carpet, it is surely now time to think again. There has already been substantial evidence that as well as in their initial role as a diabetes treatment, semaglutides – the kind of drug in question – can have a real impact on obesity for people for whom nothing else works. Now a new study has found that they don’t just help those people lose weight – they have a major effect on their heart health, regardless of how much weight they lose.

Obesity affects more than a quarter of adults, and nearly as many children – and those numbers are only going up, which brings serious consequences for public health, especially among the most deprived. So this is hugely significant news, which study author Prof John Deanfield says heralds a class of drugs as powerful as statins, “that could equally transform many chronic diseases of ageing”.

Today’s newsletter, with obesity expert and lecturer in physiology at Anglia Ruskin university Dr Simon Cork, is about what we’ve just learned, why it changes our understanding of semaglutides and whether it will mean they become more widely available. Here are the headlines.

Five big stories

In depth: ‘These drugs aren’t going to solve obesity, but they have a huge amount of promise’

Ozempic, Wegovy and Mounjaro are all brand names for a snappily named class of drugs called glucagon-like peptide receptor agonists, or GLP-1 agonists. They were first authorised as diabetes treatments, and have proven very effective. The specific GLP-1 agonist in all three is semaglutide. It works by mimicking a naturally occurring hormone, GLP-1, which is released by the gut after we eat and makes us feel full.

They don’t work in the same way for everyone, as this set of Guardian reader accounts from last year suggests: sustained healthy weight loss and a liberating release from cravings at one end of the spectrum, total failure and horrible side effects at the other. But overall, studies have shown that semaglutide is more effective than earlier generations of GLP-1 drugs, helping overweight and obese people lose about 15% of their body weight when combined with diet and exercise – much more than those who used diet and exercise alone.

“The existing studies around weight loss cover two years,” Simon Cork said. “We know that the vast majority of patients lose a significant amount of weight, and that that weight loss is associated with a drop in blood pressure and blood glucose” – both linked to heart health. “They don’t cause you to lose weight in and of themselves – to get that effect you have to have an overarching change in your lifestyle.”

It’s also worth noting that users will typically need to maintain their dose for the effects to last. When people stop using semaglutides, studies have shown, “almost everyone regains two-thirds to three-quarters of the weight back – and with that the associated health risks also return”.

What the new study tells us

The previous research on semaglutide as a weight loss treatment has largely focused on that primary role. The evidence about heart health has only been of the impact you would expect to be associated with the corresponding weight loss. But the new study, led by researchers at University College London, sets out evidence that could have a significant impact on how we think about the drug’s potential importance.

The study, which is yet to be published but has been presented at a conference, looked at more than 17,000 overweight or obese adults aged over 45 who had previously experienced a cardiovascular event such as a heart attack, and divided them into two groups – one receiving semaglutide, the other getting a placebo.

It found that those receiving semaglutide were 20% less likely to have a heart attack. Crucially, Cork said, “you can separate out the decrease in cardiovascular risk from the weight changes. We had assumed it was a consequence of losing weight – but this seems to suggest there’s a separate pathway.” We don’t know how those effects would play out in patients at a healthy weight, because they weren’t part of the study – so it doesn’t mean that semaglutides should be considered as a treatment for anyone with heart issues regardless of their weight.

At the same time as the UCL study was released, another study of a new drug, retatrutide, found that it could be even more effective – with participants losing 24% of their body weight over 48 weeks, partly because it has an impact on metabolism as well as appetite. “That can be hugely significant for someone with obesity,” Cork said. But he noted that it also demonstrated how important it is to have such drugs available under proper clinical guidance: “Someone of normal weight or who’s underweight with body dysmorphia using that could be very dangerous.”

What it could mean for availability on the NHS

At the moment, guidance published by the National Institute for Care and Excellence (Nice) says that Wegovy should be prescribed for a maximum of two years – even though the evidence suggests that when it stops being used, the benefits stop too. So another important aspect of the study, Cork said, “is that it was carried out over four years – it’s the first beyond a two-year period. It shows that the health impact is prolonged over four years, and also safe over that period. Obesity is a lifelong condition – we wouldn’t end prescriptions for patients with hypertension or asthma. So that has to change.”

Another barrier: the Nice guidelines also say that Wegovy should only be prescribed by specialist weight management services – but those are badly oversubscribed. “There has been some talk that GPs should be able to prescribe, which would reduce the burden,” Cork said.

Wegovy’s use for weight loss has already caused issues with availability for diabetes patients – and the cost of the drug is also potentially prohibitive. But even from a solely economic perspective, Cork pointed out, obesity “costs the NHS more than £6bn a year because of the associated risks – heart attacks, diabetes, stroke. So anything we can do to mitigate that has to be helpful in the long run.”

There is no instant fix to the supply issues, although these are primarily the result of private prescriptions rather than those on the NHS. “But if you look at the drugs coming down the line that are in late stage trials, I think it’s very likely that we’re going to see increased availability as they hit the market – and that will have a positive effect on the price, as well.”

What the long-term impact might be

The really remarkable thing about the new study is the hard evidence that it provides of benefits for cardiovascular health that go beyond weight loss alone. One possible impact of that is a shift in the way drugs like Ozempic and Wegovy are discussed: because of the way they came to prominence through stories of celebrities using them to squeeze into outfits, and their usage becoming commonplace among wealthy Americans who want to look good on the beach, they are now caught between being treated as miracle cures and as shortcuts to cosmetic benefits for the terminally lazy.

“That tone is very visible – you only have to look in the comments section on articles or social media,” Cork said. “People simply think the answer is eat less and exercise more – but for obesity that’s not really true.

“We can have a separate conversation about policy to prevent people becoming overweight or obese, whether it’s the affordability of healthy foods or access to green spaces – but the bottom line is that there are people who are overweight and obese because of their genetic makeup, and we have to find effective ways to help those people.”

In that context, and given the new evidence about cardiovascular impact, Cork hopes to see much wider use in the years ahead. “We have no other real way of managing obesity other than ineffective instructions about diet and exercise. These drugs aren’t going to solve the problem, but they have a huge amount of promise.”

What else we’ve been reading

As the debate over assisted dying in the UK shifts towards a majority view that the ban is an immoral anachronism, it’s really worth reading Anna Moore’s interview with the actor Liz Carr, who’s made a BBC documentary that presents an alternative argument through the prism of her own disability. This line will stay with me: “The biggest catastrophe is that we’d choose it ourselves because there was no more choice for us.” Frances Ryan gives the film five stars. Archie

Hannah Grace Deller and Esther Addley beautifully captured the journeys that NHS nurses have taken since quitting their job after the pandemic in this picture essay. Nimo

Suella Braverman has joined the long list of charities and experts who say that the two-child benefits limit should be scrapped – and on this issue, she’s to the left of Labour. By outflanking the Tories on so many subjects, Gaby Hinsliff writes, Keir Starmer has left “his party defending a frankly implausible swathe of political territory, and not just from an attack by the left”. Archie

This week’s TechScape newsletter is about the Online Safety Act, which Alex Hern describes as “quietly one of the most important pieces of legislation to have come out of this government”. Nimo

Over 100 musicians share their stories with Alfie Packham about the punishing financial landscape that has left many out of pocket and unable to pursue their musical ambitions. Nimo

Sport

Football | Erling Haaland scored twice to give Manchester City a 2-0 win at Tottenham to reclaim top spot in the Premier League heading into the last day of the season. Because Tottenham fans are unenthusiastic about Arsenal winning the league, “there was a sense around the crowd of some necessary duty being discharged,” Barney Ronay wrote – but the final result was “a serial champion simply stretching away in the straight”.

Formula One | The More than Equal initiative, a global development programme created to assist women’s progress toward Formula One and in motor racing, has announced its first selection of female drivers. The six teenagers selected will now work with a team of experienced driving coaches in an attempt to address the gender imbalance in the sport.

Rugby | Saracens have confirmed that Billy and Mako Vunipola will leave the club at the end of the season while Gloucester have also announced that Jonny May is making his exit. All three have been England regulars over the past decade but are set to join the growing number of recent Test players in moving abroad in the summer.

The front pages

The Guardian print edition leads this morning with “US warns Georgia not to side with Russia against the west”. The i has “New weight loss jab ‘gold rush’ offers obesity hope to millions”. “Anglo reveal break up plan to thwart BHP takeover” is the top story in the Financial Times; in theMetro it’s “UK’s record 3m food parcels”. The Times reports “Don’t teach pupils about gender ID, schools told” while the Daily Telegraph splashes on “Tories tell police: Bring back stop and search”. “Sex education to be banned for under 9s – and no more gender dogma” says the Daily Mail. “‘Fighting chance’ migration will fall to 150,000 a year” – that’s the Daily Express. “Mummy’s a legend … I’m a mess” – that’s the Daily Mirror, which covers TV host Ant McPartlin having a baby with his wife, Anne-Marie.

Today in Focus

Cartoon of the day | Martin Rowson

The Upside

A bit of good news to remind you that the world’s not all bad

Ncazelo Ncube-Mlilo, a Zimbabwean psychologist, has spent much of her professional career developing “culturally sensitive” therapeutic tools – the most famous is COURRAGE. Each letter in the acronym a theme in an eight-week group counselling program that encourages participants to reframe trauma as stories of survival and strength.

The program is spearheaded by her charity, Phola, which reaches more than 10,000 women, men and children in townships around Johannesburg, South Africa every year. Her method has been adopted in 40 countries including the UK, and participants have gone on to create their own support networks. “Now we are there for each other,” one participant says. “If one of us is going through something, we are just a call away.”

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