A new generation of weight-loss drugs, like Wegovy from Danish pharmaceutical giants Novo Nordisk, could have a revolutionary impact on obesity worldwide. These drugs – known as glucagon-like peptide-1 (GLP-1) receptor agonists – contain semaglutide, which mimics the actions of the GLP-1 hormone released in the gut after eating, so people feel fuller and eat less food. The drug also slows digestion and boosts the release of insulin in response to food, which helps to control blood sugar.

Until recently, the drugs were primarily used by people with diabetes, under the brand name Ozempic, as well as by high-profile figures such as Elon Musk for weight-loss. Wegovy – the new version approved specifically for weight-loss – has shown miraculous results, triggering a huge 15% weight loss after 68 weeks, in conjunction with reduced calorie intake and increased exercise. But some users complain of nausea, constipation and diarrhoea, and researchers are studying possible links to suicidal thoughts and cancerous tumours. And the drug is currently recommended for only two years, with people simply piling on the pounds again when they stop.

To assess the real-world potential of these new drugs, we spoke to Dr Stephen Lawrence, a GP and an Associate Clinical Professor at the University of Warwick. Dr Lawrence is director of the largest Masters diabetes course in the world and has served as Clinical Diabetes Lead for the Royal College of General Practitioners. As he explains, these drugs are an innovation to celebrate – but they are not a magic bullet.

What were your initial thoughts on learning that these impressive new drugs are now approved specifically for weight-loss?

My thoughts went back a great deal of time because these drugs have been around since 2009. Novo Nordisk released the first iteration of this, and it was the first (diabetes) drug that had come to market that wasn’t just weight-neutral but which offered people with diabetes the opportunity for weight-loss.

Up until then, we were using big tablets like Metformin. And we would say: look, it’s a big tablet, it’s actually a horse tablet, but it helps because you don’t put on weight. And then we’d have a smaller tablet like Glipizide and Glitazones which can make you put on weight. And then we had DPP-4 inhibitors which were weight-neutral.

But these were the first class of drugs, in the noughties, that offered weight-change. I remember thinking back in the noughties that if this works for people with diabetes, potentially it might be an option for people with obesity. So this is almost a coming of age of the GLP-1 receptor agonists.

Are these drugs a powerful new tool in the battle against obesity?

I do feel so. I think it is an inevitable occupier of that toolbox. And it will be one which I think doctors will reach for, in time, once this becomes more universally accepted. Simply because there really isn’t very much that over the years hasn’t come with its own set of issues in terms of weight-loss solutions. We go back to Rimonabant, called Acomplia, back in the 2000s, which was very effective but was withdrawn because a number of people committed suicide. And then we’ve had treatments like Xenical, which works on the gut to cause the body not to absorb fat, but then you get unpleasant side effects. And people have even tried amphetamines off-license.

But there’s been nothing really that has been anywhere near as successful as the GLP-1 receptor agonists. And for that reason, I think every legitimate prescriber will be reaching for this. Not least because patients are now very well informed. And they will be asking for it.

Is there a concern that these drugs may become too popular?

The success of the drug is almost its downfall because this is a drug which at its inception was there for people with diabetes and has become increasingly more a part of that armamentarium. So you have more and more people in the last five years in the UK that have become dependent on this drug.

There are 4.9 million people in the UK with diabetes, so you’re talking about one in 15 people in the nation. Whereas 66% of (UK) adults are either overweight or obese. So once these people access the drug, there is no pharmaceutical company in the world that’s going to be able to keep up with demand. So I think it’s great and I think it’s fantastic as a biotechnological achievement. But that has brought a whole host of not just sociological but also medical and political issues.

“When you look at the evidence it would seem unreasonable to not allow people access to the medication, regardless of whether there is a yo-yo effect or the possibility of weight regain”

Dr Stephen Lawrence

Why does this drug have such huge revolutionary potential?

Anyone who doesn’t have a weight problem may find it difficult to put themselves in the position of that person who is overweight or obese. And it’s really important to consider the psychological impact of that.

People don’t choose to be obese generally, and for society to label that as being down to a lack of self-control or gluttony is not appreciating the evidence behind this. If I eat and eat and eat, I will make myself sick, but I won’t put on much weight. I might do eventually, but I’ll gravitate back to my standard weight. Someone who is overweight might try to lose weight but gravitate back too. And there is an evidence-based theory around this ‘set point weight,’ which states that biochemically we are set at a certain level for our weight, and if we try to push one way or the other, we will eventually drift back to them.

But when people go onto these drugs, they manage to lose significant amounts of weight. When you lose anything more than 5% of your body weight, you are starting to see clinically meaningful results. Certainty at 10%. So it is difficult to argue against making this drug available to people who need it, because by virtue of having obesity, or even being at the lower end of that range, the risk of cardiovascular disease and diabetes starts to increase.

So when you look at the evidence, and the metabolic aspects, it would seem unreasonable to not allow people access to the medication, regardless of whether there is a yo-yo effect or the possibility of weight regain. Because someone’s psychological wellbeing, their success in society, their chances of getting a partner, all of this is tied up in in that perception, not just in terms of other people, but mainly in terms of how they see themselves.

Do you have concerns about possible side-effects?

Yes, I mean, certainly we know that absolutely every drug will have a license that is based on its positive attributes, because that’s why pharmaceutical companies develop them. But every drug, including paracetamol, perhaps the most innocuous of those out there, has potentially adverse side effects. We do know from history that it’s not even in phase 1, 2, 3 or 4 but in phase 5 and beyond that you start to see the less obvious side effects and adverse issues that might not have been so clear in the early stages. They are less frequent, by definition, but nonetheless they still are important.

And if there’s a fear around these drugs, it is that with the very rapid adoption of these drugs, which has been fuelled and catalysed by celebrity endorsement, it’s actually overtaken the natural development and progression of the drug. Normally it would take a number of years to get to this degree of success and popularity. But this, coupled with social media and celebrity endorsement, means you have a drug which is highly desirable getting to large masses of the population – and there are potential side effects.

The MHRA (Medicines and Healthcare products Regulatory Agency) has raised concerns around suicidal tendencies with the GLP-1 receptor agonist as a class. We’ve always known about the concern of pancreatitis – and it should not be given to someone who has a history of pancreatitis. By far the majority of people will have mild symptoms such as diarrhoea, constipation, nausea or abdominal pain, which settles down within a few weeks. But there’ll be a proportion of people for whom those symptoms become so prolonged they should not be continuing.

But when you balance that against the need to lose weight, you may find that some people think, well, I’m not going to report these symptoms, because I don’t want to be taken off the medication. So this drug has raised more questions in the way of the psychological aspects of how people interact with a drug and with a prescriber than perhaps any other medication.

Might these pharmaceutical ‘magic bullets‘”‘ encourage people to ignore parallel lifestyle and dietary change?

Yes, I do have concerns. And that’s not because people aren’t intelligent, because I think the general public is very well-informed, and social media – whilst we may castigate it for its shortcomings – really does form a very important platform for educating people and getting that message across. But the problem comes when something is celebrity-endorsed. I’m not criticising celebrities. I’m saying that this means it goes through the population very quickly – and people will focus on what they want.

I think to say that the pharmaceutical companies are at fault here would be too narrow-minded though. I think that the argument we have over whether someone is responsible for whether they have obesity or not is a different one from the aspect of saying ‘buyer beware’ – ‘caveat emptor’ – which basically states: look, if you are going to take a medication, if you’re going to put it into your body, as an adult who’s compos mentis, you have a responsibility to ensure that your read the instructions. And these do state – all of them state, so they cannot be accused of holding anything back – that the results have been achieved in combination with diet modification and lifestyle. So simply having an injection or taking a pill and expecting the weight to fall off, I think one could argue is perhaps being irresponsible. Because most of us would take some care in looking at food labels before we put food into our body, let alone a pharmacological product.

Having said that, perhaps just as we have with cigarettes, there should be a health warning on this to say: look, this is effective, however, all the trials have been put forward on the basis of it being used alongside lifestyle modification. So then people will know exactly what to expect. And also the chances of them actually going back to weight gain, to that ‘set point’, is increased if they are not managing to actually keep on with that lifestyle change.

But for some people, all it needs is for them to change from that sedentary lifestyle to doing something. And that’s the biggest step. And whilst they might not be lean, they may find that any weight regain afterwards isn’t as much as before. But all of the weight-loss drug interventions and trials have shown weight gain. So after a year, the weight starts to come up, and people go back to about 60% from where they were.

“If someone is 120kg and lose 12kg they are still significantly overweight, but they have made clinically-relevant impacts in terms of their risk of diabetes, heart disease and cancer”

Dr Stephen Lawrence

Might this drug simply help to kick-start weight loss for people with obesity?

Yes, one could argue it does give people a sense of achievement. They have managed to lose weight that they have never accomplished in the past. And in my experience of seeing patients, it makes such a big difference that they are then able to go to the gym and they are able to go out because they no longer feel self-conscious.

And even though they may still be overweight on the drug, they just feel better about themselves. And I think that’s the nuance that perhaps we can lose if we’re looking at the end game, rather than the journey towards being more healthy. If someone is 120kg, and they manage to lose 12kg, they are still significantly overweight, but they have made clinically-relevant impacts in terms of their risk of diabetes, heart disease and cancer. So I think it’s the journey that’s more important than the destination.

These drugs beg the question of where responsibility for a person’s obesity ultimately lies – with their own behaviour or with our obesogenic environment and unhealthy societal norms?

I think on a societal basis, there needs to be an open discussion around obesity. And to perhaps reset our perception with regards to blame. There’s a difference between responsibility and blame. So someone may be obese or overweight, and they may not be blamed for that, unless they are people who have overindulged. But there is still a responsibility to try and improve their health as a personal responsibility they will have for themselves. That’s no different to someone stopping smoking or wanting to take regular exercise or eating healthily. But there’s also a responsibility on society to be non-judgmental on these people.

Finally, is it possible that people may need to use these drugs for life?

As far as prescribing is concerned, if you look at the intervention policy of treating high blood pressure, treating hyperlipidemia (high cholesterol), glycaemic control and diabetes, we start people on treatment because they have dysfunctional levels. And we aim to optimise their control of their blood pressure, lipids or glycaemia. Once they get there, we don’t say: ‘Great, you’ve maintained levels now for a year or two years, so we’re going to take the treatment away. You’ve had your lot.’ And therefore it seems a bit churlish to apply the same rule to people with regards to weight loss. Because if someone struggles with weight, they are going to, in all likelihood, do so for a long period of time, in fact the rest of their lives…

So I think we should be expecting to consider this as a long-term intervention. Now, whether that be continuous or intermittent, it will be down to obviously the purse-string holders. But to say that when you’ve had your input for a year or two years, for the rest of your life you are not allowed any further intervention, I think that is probably unrealistic when you’re looking at the evidence. It’s not a personal opinion. But if you look at the evidence, and how things work out for other conditions, why should obesity be any different?