Can weight loss jabs tackle the obesity pandemic?
In this edition of The Naked Scientists, could weight loss jabs help shrink the size of the global obesity crisis...
In this episode
00:46 - The scale of the global obesity crisis
The scale of the global obesity crisis
Giles Yeo
You can barely pick up a newspaper, or turn on the radio or tv without hearing about revolutionary weight loss injections. They’ve been heralded as a magic bullet when it comes to tackling the global obesity crisis. And these new agents have also been incredibly lucrative for the people who make them. Nevertheless, health caveats have emerged, and they’re not without significant side effects for some.
So what exactly is the scale of the problem confronting us? Here’s the Cambridge-based biologist Giles Yeo, author of Why Calories Don't Count. We began by discussing exactly what ‘obesity’ means…
Giles - It's simple in some ways. Clinicians would typically define it as a body mass index, and that is your weight in kilograms divided by your height in meters squared. A BMI above 30 is considered being obese or clinically obese. The problem with that, obviously, is that it literally is just a number on a scale because it doesn't take into account anything else about how much muscle you're carrying, or your ethnicity. I think a better definition of obesity and what people are now iterating towards is carrying too much fat that it begins to influence your health.
Chris - If one looks at a population like the UK, what fraction would fit the criteria based on the traditional way of judging obesity, that BMI measure greater than 30? And what fraction fit your criteria of saying, well, it's a pathological accumulation of fat that's affecting your health.
Giles - I don't think the numbers are all that different. They just include slightly different people. the numbers within this country sit between one in four and one in three. Here it is 25 to 33% have obesity based on pure BMI. But if you then begin to think, East Asian people, people that look like me, Chinese people, and South Asian people, so Indians, Bangladeshis, Pakistanis, we famously can't get that large before we get into risk of disease. If you now take away white people, Polynesians, people who can get to quite large before they get into some risk of disease, and then you include small frame Chinese people and smaller South Asians, I think the numbers probably still bear out the same where about one in four people will have obesity.
Chris - In what way is it influencing their health? If we follow people who are in those criteria for being considered overweight or obese, what does that do to health?
Giles - Broadly speaking, we are talking about metabolic disease. The question is why that actually happens. People have misconceptions as to what happens when you gain weight and lose weight. They think that you gain fat cells and lose fat cells, and this is just not true. Your fat cells are like balloons. They get bigger when you fill them up and they get smaller when you lose weight. The safest place to store fat is in fat because they're your professional fat storage organ. The danger happens when your fat cells become full, and when they become full, the fat then has to go somewhere else and it goes to your liver, it goes to your muscles, it goes to your pancreas, it goes to your kidneys, it goes to tissues and organs which are not designed to store fat at high levels. When these tissues begin to get full of fat droplets, your liver becomes like fois gras, for example. It begins to influence the function of that organ. When that happens, you then tilt into metabolic disease. This includes stuff like type two diabetes. It could include fatty liver, it could include high cholesterol levels, it could include high blood pressure. Each of us has differing amounts of fat we can store safely. We each have different safe fat storage capacities.
Chris - And when a person puts themselves on a diet, does that actually reverse that state or do you lose the fat from the adipose tissue where you would normally store fat first and leave behind the bad fat stored where it shouldn't be? Or is it the other way round?
Giles - Now, it depends on how long you have been fat for. Your liver, for example, filling with fat and then disappearing, it's actually a relatively normal thing to happen. So in other words, if you had a big gigantic meal and you ate lots of rich food, you will get some fat in your liver because that's almost its natural state of affairs. When you lose weight, or when you stop eating, then the fat disappears from your liver and it tends to disappear from your muscles as well. Now if you then end up with a situation where you've been fat for so long, or you've had obesity for so long and it begins to damage the tissue, such as damaging your liver and what have you, well then you end up with longer term disease even once you've lost weight. So really it depends how long you've been carrying that extra fat for.
Chris - We're brewing up two problems, aren't we? We're brewing up an obesity crisis because lots of young people are getting fat, but we've then got health problems caused by long-term overweight.
Giles - Yeah, that's true. Because actually it is seldom obesity itself per se that is the problem. I mean, there are issues with being too large, there are issues of gravity, arthritis, sleep apnoea (that's the inability to breathe properly at night because of the sheer amount of fat that's on your chest, for example), and immobility. But what actually kills you are these associated metabolic diseases. Type two diabetes, high blood pressure. And the issue is, particularly if you get obesity young (and we are seeing increasing numbers of young children with obesity) then you spend longer in life with these diseases. If you're now getting the disease as children, you now have to spend 70 years of your life suffering from those conditions. It's a problem at many, many stages.
Chris - But do we actually have the data, Giles, to say, well, if I am continuing to live the lifestyle I was living that got me overweight in the first place, but I take these injections or these drugs and they cause me to lose some weight, but my lifestyle remains the same, does my disease risk actually change with that? Or do I maintain the original disease risk because my lifestyle that is bad for me has continued, I'm just getting away with it.
Giles - That's an excellent question. I think, just by losing the weight, just by reducing the amount of fat, which is what these drugs will do, you will have a health effect. That is going to have a health benefit. But you're absolutely right, if your diet was not so great to begin with and you ate lots of chips and cookies and Oreos or whatever it is you were eating, then all you're going to do is eat less of those items. They're not going to actually improve your diet. In fact, if your diet was so rubbish to begin with, and so therefore you had to eat quite a lot of it to make sure you had enough micronutrients and protein and what have you, suddenly you take these drugs and these drugs are so effective at making you feel full you just eat less, you could actually, depending on how rubbish your diet was to begin with, tilt into malnutrition. These drugs should not be used in isolation. They shouldn't just be given out, they should be prescribed and they should come with a suite of wraparound treatment, shall we say. This includes some form of dietary advice or intervention and probably some form of exercise regime as well to prevent you from losing too much muscle mass. You are absolutely right, the drugs do one thing and one thing only. They make you feel fuller and so you eat less. You still have to improve your diet, you still have to improve your lifestyle, for lack of a better term, your behaviour.
Chris - So there's no free lunch then?
Giles - There is no free lunch. And I think we have to get the messaging right because these are very, very effective. Don't get me wrong. They're very, very effective drugs and they should be used, but we still need to improve what got you there to begin with in order to make sure you sustainably remain healthy.
09:34 - What is it like to get a weight loss injection?
What is it like to get a weight loss injection?
Miranda Levy
What’s it like to take a course of these weight loss jabs? Journalist Miranda Levy has recently written about her own experience in The Daily Telegraph. Following a bout of weight gain due to antidepressants she took some years ago, Miranda became increasingly interested in getting back in shape. So she decided to explore weight loss injections with the agent Mounjaro, which also goes by the name Tirzepatide. Like other injected weight-loss agents, it’s only available on a paid-for, private basis. And it’s pricey. Her experience was also not altogether positive…
Miranda - I'm a health journalist. I've been following the genesis of the GLP agonist drugs, although they've now developed one stage further, haven't they? I thought, well, that's interesting, but not for me. Oprah Winfrey's doing it, come on, it's going to be another flash in the pan scam. But, increasingly, following the literature, the studies being published, and also talking to doctors in my family, my brother's a professor in endocrinology and was starting to say, 'You know what? Actually, these drugs could be really good for you.' We've had colleagues who've been on them, they've done wonders for these colleagues. They've lost X amount of weight and this could be a good thing for you to try.
Chris - What was it like? When you get that jab, then what happens next?
Miranda - So I turned up, there was a very charming young doctor, handsome, very disarming. He did the injection, it was fine. I'm not particularly squeamish about things like that. Then he said, great, here's the box, here are the anti sickness pills in case you need them. That'll be an extra 20 quid. I said, okay. And then he said, 'I'm going to weigh you now.' And I thought, that's a bit weird. Maybe you should have done that beforehand. But fine. And off I went and I was really excited. I thought, I'm doing something about this. I feel like a bit of a medical pioneer. I'm going to write about this. It's going to be amazing. Then, I got home and I looked at the box and I rang my brother and my sister-in-law to tell them. I said, I've got my 7.5's, and my sister-in-law went '7.5? That's a bit high. The guidelines are normally to start at 2.5 milligrams.' So, in other words, that's three times the recommended dose. I went, 'really?' And sure enough, I'd been given three times the recommended dose, and 12 hours later I started to know about it.
Chris - In what way? What was it like?
Miranda - I probably started to feel a bit queasy before going to bed, but I had more or less a normal dinner. I woke up, went to have some breakfast, just made myself a piece of toast and jam and a cup of tea. I just could barely look at the toast. There's one thing to say you lose your appetite, but I could hardly put any in my mouth. I made myself eat two bites. I couldn't even drink my tea. I had a sip of tea. If anyone listening has ever been pregnant, it felt very much like morning sickness. But as the day went on, it didn't get better, it got worse. I could hardly eat a thing for a week and was really, really nauseous.
Chris - So it just made you feel so bad. I suppose, in that respect, it was probably helping to lose some weight, wasn't it? Because you just weren't eating anything. But it's not terribly compatible with having an active life or doing work if you feel starving hungry and sick all the time.
Miranda - It was intolerable, really. It's a little bit frightening, you know? It's not like you've had food poisoning or you've been on a car journey and you feel a bit sick and then it's over. It went on for days and days and days. As I also wrote in the article, I very quickly got back to the clinic and told them this was going on because it wasn't acceptable to me, now that I had more facts at my disposal and I'd been given too much.
Chris - Were they receptive to you going back to the original plan that you'd hatched with them, which was, well, we'll cut the dose down then?
Miranda - The short answer to that is no. I got back in touch with them on the Friday, so I'd had the jab on the Thursday, so it was by Friday afternoon. I rang the clinic, sent them an email as well, and they say the doctor is on leave. He's not back till Tuesday. We're closed till Tuesday. I had to cope with the whole weekend of feeling like this. Tuesday afternoon, I rang and emailed and was stonewalled. Finally, the receptionist answered. I had no reason to be angry at that point, really. I just said, 'look, actually this plan isn't working. I realised I'm on three times the normal dose? I'd like to go back to the 2.5, please, as we discussed. The receptionist hedged and hummed and mumbled. And then she said, 'well, I'm not sure we could get that for you.' And I said, 'what do you mean?' She said, 'I'm not sure the pharmacist can get the 2.5.' And I said, 'right, I'm coming to the clinic. I'd like to talk to the doctor face to face, please.' I just jumped in my car and went there and they said, 'no, you are misreading the papers.' They were very patronising. They said, 'you've read that this is the starting dose for type two diabetes. This is weight loss. There've been X clinical trials that show you that's not the starting dose for weight loss.' You know? I felt a bit steamrolled really. I didn't want to start a screaming row while I was there. So I said, 'look, whatever the studies say, I would like to go back to 2.5 please, because this is not working for me.' They basically said, 'no.' And I said, 'what do you mean no?' And they said, 'it won't work for you. We won't do that.' I said, 'what? You won't do it?' And they said, 'we won't do that.' And I said, 'well, in that case, this isn't the treatment for me and this isn't the clinic for me.' And they looked very, very surprised at that.
Chris - Is it still not the treatment for you? Have you gone elsewhere or have you tried other treatments, or have you decided this is just not going to work for you, taking these sorts of drugs?
Miranda - Good question. For now, I'm trying something else. I left with a quite dim view of the clinic, but I'd lost four pounds in a week. So once I started to feel better again, I thought, this is great. I want to continue this. So since then, I've decided to really go for it with diet and exercise because, interestingly, I found this inspiring and a springboard. It's working. But maybe if it's not working enough, at some point in the new year, I might go back to Mounjaro, armed with this knowledge and how to do it safely.
Chris - So your take home message for anyone who's listening to you is, go into this with your eyes open, make sure you know what you are getting into and be prepared for the fact that it might not work for you. It might be pretty horrendous. It is not a simple walk in the park and you may have to change things.
Miranda - Yes. Be informed. Know what the starting dose should be. Have informed consent. Stand your ground. Know when to say no. Know when to ask questions. And also do expect some side effects because there are some side effects, but they generally are not nearly as severe as mine and they don't last as long.
How do weight loss jabs work?
John Wilding, University of Liverpool
How do weight loss injections actually work? John Wilding is a professor of medicine at the University of Liverpool and has published widely on these agents…
John - Clinically I trained as a doctor working in diabetes and endocrinology, which is to do with glands and hormones and so on. And during my training I saw lots of people living with Type 2 diabetes, which is a condition which is largely caused by obesity. And then I spent some time working in a laboratory trying to understand what it is that makes people eat more or eat less and why some people develop obesity and some people don't. And one of the things that I did in that laboratory was seeing whether different chemicals in the body, different hormones, affected body weight. And one of the things we discovered was that with this hormone that we already knew was involved in controlling sugar metabolism also is an important signal after we've eaten to tell the brain that we're full. So that got me really interested in this as an area that might help people with obesity as well as diabetes.
Chris - What hormone was that?
John - This was a hormone called Glucagon-like peptide-1, or GLP-1 for short, which is actually the basis now for treatments for both Type 2 diabetes and treatment of people with overweight and obesity.
Chris - Where does it come from in the body? Where does it go? In the body and what does it do?
John - GLP-1 is actually made in the small intestine, so it's made in the gut and it's produced when we eat. So when we eat, the GLP-1 levels go up. And it goes around in the bloodstream and it goes to two main places where it has its actions. One is the pancreas where it tells the pancreas to make a hormone insulin which controls the blood sugar after we've eaten. And the other thing it does is it goes to the brain where it tells the brain, 'Hey ho, you've had some food. It's time to slow down and eat a bit less now, otherwise you're going to start feeling too full.'
Chris - So these drugs which mimic that action, they're basically telling the body, 'stop eating you've had your fill.' It's as though you've had a big meal and you haven't.
John - That's exactly right. And of course it's one of many hormones from the gut that do the same thing. It's one of the important ones. But we know that there are at least half a dozen other chemicals from the gut that are performing that function.
Chris - And when we use these agents, are they actually effective or in the same way that if you flog a system very hard by giving it fake signals, eventually it becomes deaf to them and ignores them. So does that happen with these drugs or, when you use them, does the body remain sensitive to them and so they do drive a fullness sensation and therefore a reduction in calorie intake?
John - Yes, so these medicines are based on the natural hormone GLP-1, but they've been chemically modified because if we give the natural hormone, which we actually did in some of those early experiments, it only stays in the body for about three minutes because it has been produced continuously by the intestine. So these drugs make that long acting and the first drugs maybe you had to give by injection twice a day, the later ones once a day, and now we've got drugs that we can give once a week. So these drugs last a lot longer in their effects than the natural hormone. And they're also much more powerful. We do know from long studies going on for at least four years now in people with diabetes and in people with obesity, that these drugs continue to work with both actions, both to continue to stimulate insulin secretion and to continue to signal to the brain that feeling of fullness even after you've been taking them four years.
Chris - If you've got something that is promoting the release of insulin though, and you are not eating enough because you've suppressed your appetite because your brain is now being told you are full, do you not end up with lower blood sugar? And is that not a bad thing?
John - No, that's one of the very interesting things about this hormone because the way this hormone works in the pancreas is that it only stimulates insulin secretion when the blood sugar is high. When the blood sugar drops to below normal levels, it stops working. So there's a built-in safety mechanism there, which wasn't there with some of the older drugs that we used to treat diabetes with.
Chris - And how good are they? When we start a course of this stuff, how effective is it at suppressing calorie intake first and foremost, and how does that translate into weight loss and over what sort of time course?
John - So there have been some short term studies that have been done that have looked at people who've taken the drug for a few days to build up the levels in the body and then looked at how hungry they feel in a short term laboratory setting. And people tend to eat about two thirds of their normal meal size. So that's quite a big reduction in their energy intake in these acute situations. It's probably not quite as strong as that in the real world. There are lots of other temptations and so on around, but what we do know is that with the more recent drugs, particularly ones like semaglutide and Tirzepatide that are given once a week, we see people lose weight over a period of about six months to a year. And then usually the weight reaches a steady state after that. But that weight loss is around 15 to 20% of the original body weight. So if you start off at a hundred kilos on average, you might expect to get to between somewhere around 80 and 85 kilos after taking this medicine for a year. The reason why it reaches a plateau, of course, is that as you get smaller, your body needs less energy and that means that that lower food intake eventually matches your new lower energy requirements. So eventually you stop losing weight, which is a good thing because otherwise we disappear into nothing.
Chris - <laugh> indeed. But on that note, one of the things that we try to emphasise is remaining fit and active because the more lean tissue, the more muscle you have, that's where the energy's being burned. You want to shed the fat. So when you take something like one of these drugs, does it lead to preservation of the lean tissue and loss of the fat, or do you end up sacrificing both?
John - We've actually looked at this in some of the studies that we've done, particularly with semaglutide. And what we find is that if you lose 15 kilos, you might on average lose about two thirds of that and the rest is lean tissue. That includes water and muscle and everything else in the body. We can't separate exactly muscle. That happens if you lost 15 kilos by going on a diet or if you lost even more than that by having bariatric surgery. Whatever way you lose the weight, that is about the proportion that happens. So you don't lose any more probably, and you probably don't lose any less when you're taking the drug, than if you lost weight with other means.
24:30 - Can public policy tackle obesity?
Can public policy tackle obesity?
Dolly van Tulleken, University of Cambridge
Drugs aren’t the answer to everything obesity-related though; arguably, changes in lifestyle, diets and activity levels have played a massive role in creating the obesity pandemic in the first place, which means that effective policies around exercise, public health, and what we eat are crucial if we’re to halt the trend. Dolly van Tuelleken is from Cambridge University's MRC Epidemiology Unit. She told me why, compared with yester-year, waistlines are bulging more than any other time in human history…
Dolly - The vast majority of our diets would've been made up of essentially whole and minimally processed foods, foods that you would recognise as having maybe grown in the ground or come from an animal, et cetera, et cetera. Maybe processed a bit, so we would have foods such as milks and cheeses. These days though, we have seen the huge ultra processing of foods to almost an unrecognisable state. So you can look at ingredients, lists of packets of food in the supermarket today, and there might be not even anything in the ingredients list that you would recognise or just a handful of many of the ingredients that we've recognised. So we've had this huge ultra processing industrialisation of our food system, and that has basically led to an enormous rate of diet related disease and food related ill health in that time. And that's for all sorts of reasons. That's because these highly industrialised foods often contain ingredients and additives that we are slowly starting to find out have very harmful effects on our health. They are designed purposefully in a way to be hyper palatable. That delicious, almost addictive quality. They are also designed to be over-consumed. And that's not just the food itself in the way that it's designed, it's also the way that the marketing is designed and the fact that you can have 'buy one get one free's on unhealthy foods, which we know isn't about giving people, out of kindness, more food or food for free. It is about making sure that people consume more and more of those products and have that familiarity with those products, those products built up over time. So there are lots of techniques and strategies that the largest food companies in the UK use to make sure that people consume as many of their products as possible. And unfortunately, the majority of those products that they sell are unhealthy.
Chris - Do you not feel a bit uncomfortable, then, that we're in a position where we're having to invoke drugs, jabs, injections, pills in order to combat what is effectively a marketing success? We've basically made food over-addictive, over-calorie rich, and people are overeating it as a result, and now we're having to compensate by giving people injections.
Dolly - Yeah, I mean it's a very bleak way to put it. I was having a conversation recently and the idea of a kind of corporate solution by big pharma to a corporate problem made by big food was discussed. And that is another pretty bleak way to look at it. Essentially you've got huge industries that are making, um, a lot of money from treating a problem that another group of people in companies are making a lot of money from. So it is sad, but it's really important to provide treatment to people that need it. We are where we are in terms of the system that we have, the food system that we have, and the health consequences of that. So it's really important that no individual is penalised for being part of that system. And if their health has been affected, then they should absolutely get access to the treatment needed. But in order to tackle this issue, I don't see treating our way out of it as the solution. We cannot treat them and send them back to the conditions that made them sick in the first place. We have to see essentially a transformation of our food system so that it enables good health for everyone.
Chris - That effectively means policy, doesn't it? It means we need healthy food, and healthy eating policy, and something has got to change. So what is the nub of that? Where do we go in order to exact that? Because governments have been told for decades that the population are becoming overweight. This is becoming a huge drain on resources. It's very unhealthy for them. They know that. Why have they not been able to do anything? It can't be an easy nut to crack.
Dolly - The UK government has been trying to tackle obesity and food related ill health for decades. It published its first obesity reduction targets in the early 1990s, and you won't be surprised to know that they never reached the targets. But since then, we've basically had government, after government publishing strategies containing literally hundreds of policies. We've had 689 policies published by the government to tackle obesity and food related ill health since the early nineties. So a huge number of ideas were proposed. And, and behind that, I would absolutely say that politicians and governments have wanted to tackle this. It's not that there's necessarily a lack of will to do that in government. There has been a tension on this, but it is a very difficult problem to solve. Part of it is because policies are so rarely fully implemented, and there are lots of reasons why that is, but there are lots of good ideas out there. It's just that the nature of government and the politics of it means that ideas don't get seen fully through and we'll either have the same ideas proposed again and again, delayed, scrapped, introduced but weakened. That happens time and time again. And we're seeing that at the moment. So implementation is one of the biggest problems. The second is that the government has tended to try and focus on getting people, individuals, to change their own behaviour without making that easy by shaping the environment around them. And we know that that doesn't work because essentially you are telling people to change their behaviour in a situation that makes it incredibly difficult, and in some cases almost impossible, for people to do that. But I would say on a positive note, we've had more governments in recent years proposing more policies that seek to shape the environment, to make it easy for everyone to live a healthy life.
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