**Jim Hill:** Welcome to “Weight Loss And…”, where we delve into the world of weight loss. I'm Jim Hill.

**Holly Wyatt:** And I'm Holly Wyatt. We're both dedicated to helping you lose weight, keep it off, and living your best life while you're doing it.

**Jim Hill:** Indeed, we now realize successful weight loss combines the science and art of medicine, knowing what to do and why you will do it.

**Holly Wyatt:** Yes, the “And” allows us to talk about all the other stuff that makes your journey so much bigger, better, and exciting.

**Jim Hill:** Ready for the “And” factor?

**Holly Wyatt:** Let's dive in.

**Jim Hill:** Here we go. Holly, today we're going to talk about type 2 diabetes. In the U.S. alone, there are over 22 million people who have been diagnosed with type 2 diabetes, and another almost 100 million with prediabetes, which means they're at high risk of developing diabetes. And these numbers are probably an underestimate because many people aren't aware that they have diabetes or prediabetes. We know that obesity and type 2 diabetes are very closely related, and the majority of people with type 2 diabetes are overweight or obese. We also know the many benefits of weight loss. We've talked about lots of those in our podcasts, and today we're really going to focus on the benefits of weight loss for people with type 2 diabetes, pre-diabetes. What can weight loss do? So to help us understand this, we have truly one of the world's experts in this area, Dr. Mike Lean. Mike is chair of Human Nutrition. He's based at the Glasgow Royal Infirmary in Scotland, where he is a physician. His primary training was in medicine at Cambridge, and he has a degree in history and philosophy.

His medical training was at St. Bartholomew's Hospital and postgraduate training in Aberdeen and Cambridge. Recently, Mike, along with his longtime collaborator, Professor Roy Taylor, have been awarded the 2024 Rank Prize for Nutrition for transforming the lives of thousands with their groundbreaking work on dietary approaches to type 2 diabetes remission. We're very lucky to have someone that really understands this topic. So, Mike, welcome to Weight Loss And.

**Mike Lean:** Thanks very much, Jim. And you should add to your preamble, of course, that I also learned a little tiny bit about obesity from a spell in Denver with you and with Holly a few years ago. And these are all part of forming a kind of career you pick up in a career. You learn things. You observe things. Sometimes you have to file them away for years and years and it kind of you can't act on them until the conditions are right. And that time I spent in Denver allowed me to think hard about things I'd seen in the past and to fuel myself to go ahead and do new work in the future. And we had a good time playing tennis and climbing mountains, so, thanks.

**Jim Hill:** Well, he climbed just about every mountain in Colorado, but he did spend some time working on research, and it was a fun time, Mike.

**Holly Wyatt:** I guess, maybe let's get started. So can you briefly tell us a little bit about your academic journey, what you're currently doing, and then we'll jump into the hard questions.

**Mike Lean:** Yeah, okay. So going back to what Jim was saying, the link between type 2 diabetes, prediabetes, and obesity is something we've known about for many, many years. And we kind of shuffled around the, I think, very obvious fact that this is a causal relationship. People don't get type 2 diabetes unless they put on weight. We've been a bit bamboozled by the fact that we've customarily said, oh, you're not overweight until you have a body mass index of 25 or not obese until you have a BMI of 30. That is to misunderstand the disease process. And I think my work over 30 odd years has allowed us to begin to say, hang on, this is the same disease process. Putting on weight is the disease process of obesity, which is excessive fat accumulation, body fat accumulation. It's excessive or abnormal fat accumulation. And it doesn't require a particular cutoff. You don't have to be visibly obese, visibly overweight in order for it to start doing damage. And that's probably what I've discovered. That's one of the things that I kind of stumbled across many, many years ago, that some of our people with type 2 diabetes are not hugely overweight, but we recognize that they had fat in the wrong places. They had begun to put fat into vital organs where it does damage.

So that perhaps is the most fundamental thing. That took observations for many, many years, which we've firmed up on. That allowed us, for example, to observe that the waist circumference is a much more important guide to diabetes and to its consequences than the body mass index. The body mass index has been sort of adopted worldwide as a descriptor. But of course, somebody with a high body weight, high body mass index, or BMI can be very muscular. What actually matters is where you, if you have excess fat, where you put that fat. And it looks like at a certain point, people will start to put excess fat into vital organs. And those are the liver, the pancreas, the heart, your skeletal muscle, your muscle. And they all tend to happen about the same time. And it doesn't happen at the same point for different people. So Asian people tend to put fats into their vital organs at a much younger age and with less total body fat. So they would have a low body mass index if you like. But they often do have the big waist circumference as a guide to it. So we're looking at a disease process which affects probably 30 or 40 percent of all human beings. If they put on weight, they will start to put it into the wrong places and we'll get type 2 diabetes, hypertension, and this sort of raft of chronic diseases which ultimately lead to earlier death, etc. And I suppose the other thing we've tweaked, Jim, and we're now able to say more loudly because we have a solution, is that type 2 diabetes when I was a medical student was considered an inconvenience of old people. Take a pill, come back in a year's time and that was how it was viewed. It was not considered to be a big disease alongside heart disease or something like this now with better epidemiology and understanding the disease process and with what we call the coca-colanization of our globe where fast food ready food, there is no shortage of food, no shortage of calories or very few places where there really is a big shortage of calories in the least industrialized world. With that, people are putting on weight younger and they're getting their diabetes younger. In the UK, the average age of onset of diabetes is now 50. And I believe it's a good bit lower than that in the United States. And people who develop diabetes under the age of 40 are going to lose somewhere between 10 and 15 years of life. It kills. This is a disease killing worse than breast cancer. I mean, most people would think breast cancer is a pretty bad disease and you do something about it. You probably would take quite nasty treatment for quite a long time to get rid of breast cancer. Type 2 diabetes in younger people is killing and is disabling probably more than breast cancer and yet we haven't sort of adopted within the medical profession, we have not really taken it on board and said this is an equally big disease. We need to take the treatment equally seriously and that's a big message. I mean across the board if you develop type 2 diabetes, on average, you'll die five or six years younger.

**Jim Hill:** Plus, it's a debilitating lifestyle. There's so much you won't be able to do. Even before you die, you're going to be debilitated in many, many ways. It's going to reduce your quality of life.

**Mike Lean:** Absolutely. If you get into diabetes when you're 70 or 80, you probably don't need to worry about it too much. Okay, Jim, you'll be all right. However, if you get it younger, you really should be worrying about it. And you should be prepared to take treatment very seriously. And that treatment to get rid of the disease is dietary. The medicines we have, we've got many hundreds of medicines which are available worldwide. There are dozens of medicines licensed in UK and in the United States. They do have a benefit. There's no question about it, but they don't take away the disease process and that continues.

**Jim Hill:** So this is an important concept, Mike. So right now, probably in the U.S., if you go in and get diagnosed with type 2 diabetes, your physician is going to put you on medication. And many of those medications actually promote weight gain. And it's a game of just trying to keep things from getting worse. That's what the medications do. What you're saying is there's a different way of doing it to get at the cause of this rather than to try, usually unsuccessfully, to permanently manage the symptoms.

**Mike Lean:** Yeah, you're right. I mean, I think if you're diagnosed with diabetes and you have a half-decent doctor, he or she will say, you really need to take care of your diet and to try and lose some weight, but we'll start the medicines today. And that kind of puts the whole focus on medicines. People believe that the medicines are very important and they place them in their sort of priorities above the diet and lifestyle.

That's the wrong order. The medicines are, you know, they're good and the modern medicines are extremely good. They're hideously expensive, but they are effective. However, they don't stop the disease process. And this is because the damage to our tissues, and we're thinking particularly here of the pancreas, which makes insulin, that damage is caused by fat accumulation. And that starts to accumulate when the fat is also building up in the liver, in the heart, in other organs, which are going to fail. And that's our research in the DiRECT trial, amongst other things, showed that if people lose enough weight to be clear of their diabetes to get rid of their diabetes what that has done is remove completely the extra fat from the liver from the pancreas and it allows the pancreas then to start to regenerate. So a person with type 2 diabetes has approximately half the capacity to make insulin at the time it's diagnosed. And when we took up our patients at baseline, these are people very typical people with type 2 diabetes, we tested them by giving them glucose intravenously to give them a big hit of glucose plus arginine. Their pancreas could not make a normal amount of insulin. It was half of normal. That's why they have diabetes or part of the reason they have diabetes. When they lost weight, they got clear of their diabetes, the fat in the pancreas disappeared, and gradually over two years their pancreas regenerated, grew in size, and was then able to make a normal amount of insulin again. So you know we've kind of undone the entire disease process, if you like.

Now, usually by the time it's diagnosed, people have had diabetes for quite a long time, often for years, and it's already started to do secondary damage to the organs. So I think the big message now is that we need to identify people as early as possible and offer them perhaps a really radical treatment, which would be to say you're going to have to lose enough weight to be clear of your diabetes. And your distinction at the beginning when you spoke about pre-diabetes is really important because people with pre-diabetes don't yet have the pancreatic damage to have the blood glucose, the hemoglobin A1C, which we then say you now have diabetes. But they do have extra fat in their heart, in their muscles, in other tissues, and it's already doing damage elsewhere. So this is part of a multi-morbid disease pattern.

**Jim Hill:** So Mike, I want to dive a little deeper into that. Mike talked a little bit about the DiRECT study. This is a study he and his colleagues conducted. I know you published a follow-up. Tell our listeners very briefly what you did in that study and why the results are really paradigm-shifting in how we approach type 2 diabetes.

**Mike Lean:** Yes, thank you. I mean, over the years, I had observed individual patients who were able to lose weight and did lose weight, and their diabetes seemed to go away. Other doctors, nearly every doctor has seen these patients. And the prevailing wisdom was these are very unusual people, and their diabetes was obviously not real diabetes. And it was assumed that that would not apply to most people with diabetes. They're told to start with tablets, to stay on the tablets. However, because I'd done research previously in body fat and body fat accumulation, I had twigged that people with type 2 diabetes have excess fat in not just the pancreas and the liver, but in other places too. And all these organs will malfunction with fat, and they'll all get better when you get rid of the fat. I then thought, well, hang on, let's see if we can actually prove that losing enough weight will cause diabetes to go away. And so what we did, and it took years to persuade the funders to agree that this was remotely possible. I was considered a bit of an old doctor considering this was even remotely possible. But finally, we did get the funding.

That was about 2010, 2011. What we did was we went out into primary care in the UK. This is all in the National Health Service. Ordinary people with type 2 diabetes up to five or six years, up to six years from diagnosis. And we said to them, we believe that at this relatively early stage, it should be possible to reverse this disease to get a remission of disease if you can lose enough weight. And we then designed, and this took us about 10 years, a diet program, which would allow us reliably to get 10 or 15 kilograms weight loss. And so we got funding to do this. And we went into primary care, we equipped the nurses, and if there were dieticians, the dieticians there to administer a diet program. Program doctors were really not involved at all except to check on the medications and if they did need to change the medications to do that. On day one we asked our patients to stop all their diabetes medications completely and that is because they were going to go on day one onto a diet program that will cause them to lose weight and the risk was then they would get, hypoglycemia and get into trouble if they continued the medication. Also our patients quite like the idea of stopping medication. The other thing radically we did was to say you must stop all your blood pressure medication and diuretics if they're for high blood pressure because, if you go on to this diet program, your blood pressure will drop substantially and there will be a risk if you carry on medication of postural hypertension.

People have blackouts, crash their cars, injure themselves and we didn't want that either. Also patients actually like the idea of stopping these drugs they've been taking for years if they could have an alternative. So they then went on to a diet program. And what we used after a good deal of research into this was a formula diet, which is really very like the formula diets that you can buy and obtain from elsewhere, for 12 weeks. And it was an 850-calorie formula diet, so not very low-calorie. And it was complete in vitamins and minerals, so it's entirely safe. And the notion was that they do this for 12 weeks. And if they followed it, they would lose at least 20 kilograms in weight. We knew that they wouldn't because they don't take the disease seriously enough yet. But we argued that if we aimed high, we would get better results along the way. What we actually got in that time was about 14 kilograms weight loss on average. So half the patients lost more than 14 kilograms, half of them less. So they did vary in how they applied themselves to this. And just as an aside, during that time, we stopped their blood pressure medications. On average, their blood pressure all fell by 10 millimeters of mercury, a huge fall in pressure. So that was really important. And we didn't see any rebound increases. So doctors should be reassured that if they want to treat their patients with high blood pressure, well, stop the medication, put them onto a diet, but make sure they follow the diet because that's the trick. So that was getting the weight loss was surprisingly easy.

Not everybody could do it, but the majority did. And they didn't complain of hunger, which is interesting. thing. They complained more of being bored and that their social commitments got in the way of this. Again, I come back to this. This is a very serious disease. Would you say that for your cancer treatment? Would you say, oh, my social commitments have gotten in the way, so I've stopped the treatment? No, you wouldn't. And we're going to have to bang that drum again and again and again. This is a big, serious disease. But over half the patients lost 14 kilograms. And our target of trying to get them all to 15 didn't work, of course, but it got quite close to a large number.

**Holly Wyatt:** So let's stop for a second and make sure that I think the listeners know what's going on here. So it sounds like, you know, a lot of our listeners are here in the United States. So let's turn that into pounds for them. So it sounds like around 30 pounds ish. Is that okay? 30 pounds of weight loss. And they did this by a diet that was about 850 calories a day. Was it liquid? Was it all a liquid?

**Mike Lean:** The diet program was sort of known as soups and shakes. So it was, you know, you make them with a good, and there was a milk allowance and they were encouraged to have lots of fluids to maintain hydration. Also, we advise them all to take a dietary fiber supplement because with that 850-calorie diet, if you continue that for a period of time, constipation would otherwise result. And that was one of the sort of immediate consequences.

**Holly Wyatt:** So technically not what we call a very low-calorie diet, right? We're less than a thousand; 850 calories. They can do it. It sounds like they could adhere to it because of the shakes and the soups. And it was like, here's what you eat and you're not going out there and you're eating what's provided to you. And they lost around 30 pounds with this.

**Mike Lean:** Yeah, they didn't. I mean, the diet is kind of boring. It's coming out to soups and shakes. You don't go back to second helpings. It's just not a gourmet design. And that's part of the principle here. And during this time, we use that time while they're losing weight to then say, look, the end game here is how you're going to modify your eating pattern after you've lost the weight and how you're going to make changes from what you've done for the last 20, 30, 40 years. And that takes a lot of learning. That takes a lot of guts and commitment to say, I'm going to buy different things. I will have different things in my fridge. I will not have, you know, I was going to poke a finger at people I know who have a fridge full of ice cream in their house. That just is not compatible with getting rid of your diabetes. And you have to say, make some changes. Some of them are quite big changes. So if it were one of those households that has a fridge full of ice cream, I'd have to say, ice cream is fat and sugar mixed up together. That is exactly what is causing this problem. Well done the food industry, well done marketing with all their flavorings and colorings and everything. For you with type 2 diabetes, this is a much bigger problem. You have to say no to that. Just take that fridge out of your house and instead have somewhere to have nice fresh fruit and the rest of it.

**Holly Wyatt:** I want to get you back on the story though, because you were doing good. You're on a roll. I liked it. I just want to make sure our listeners are staying up to date. So now they've lost the weight. How long did it take them to lose the weight? How long did they, on average, did they take to lose the 30 pounds?

**Mike Lean:** They were on the diet program for notionally 12 weeks. Some of them stopped early. Some of them stopped sooner than that. Those who stopped very early clearly were not committed, and they actually did much less well early on. Those who stayed with it and lost 10, 15 kilograms, did incredibly well, and they were able to maintain the weight loss for up to one year and up to two years and beyond. And what we learned from that is something really fun about it.

People who have been on a diet and they've lost five kilos ten pounds you'd say well that's well done medically that brings certain benefits. But you don't look any different. You don't feel any different. And it's really hard work and what's in it for the people who've done all that and very often they don't see the benefit and they put the weight back on again. If you lose 30 pounds and you get rid of your diabetes, wow that's a big deal that's a really big deal, and quality of life was strikingly improved. We measured it using conventional tools. It's quality of life. People felt better. They felt better about themselves. And they felt more inclined to stay with the plan if they were able to get this quite big weight loss. And that improvement in quality of life continued for five years. That was not a fluke. That was really important. And I think we've kind of badgered people to lose the five kilograms, and that's what they were able to do. And we tell them that's a success. That's not a success.

**Jim Hill:** We know that. That doesn't work. The doc thinks it's a success, but the patient is sitting there saying, this is not anywhere close to what I wanted to lose. So Mike, what about the diabetes remission? What did you find?

**Mike Lean:** Yeah, so we monitored our patients quite closely in this. And we were able, what we said was, we're going to stop your medication. We will keep a check on your blood glucose every two weeks and every four weeks. And then when it was all stable, we relaxed a bit. And if necessary, we did put them back on medication. But the great majority did not need to go back on medication. And at the end of the year, we had half of our patients, 46%, half of them were free from diabetes off medication. Another 20% or 30%, were still diabetic, but they had managed to remain off medication with their hemoglobin A1c very close to normal. And of course, we then urged them to try and lose weight. They found it really hard. People who had not quite made it found it really hard to have a second bite of this. So really the message there is to do it really well the first time around because the second time around is harder. So at the end of the year, 46% were free from diabetes. Now, that's a colossal proportion. It exceeded, it doubled, more than doubled our highest expectation, which was to say we were told if we could get a 20% remission rate then we're going to have to change how we manage diabetes nationally. The whole way we treat this disease has got to be changed if 20% can get remission in one year. In fact, 46% got remission in one year.

That national change started almost right away. What happened then at the end of that year, they went into a maintenance program with just every two months and then every three months. They were called up by their nurse or dietitian to say, how are you doing, and try and keep them on the target. At the end of two years, out of the 150 patients in our intervention group, 15 of those who got remission had let it slip and their weight had gone back up to within 10 kilograms, that's 20 pounds of their baseline. And they regained their diabetes. And we were able to show that those individuals who had once again relapsed into diabetes had regained the fat in their liver and in their pancreas. And this is what told us that it is that fat which is lodged in the liver, in the pancreas, which is doing the damage, which is causing this disease and all its complications. So that was quite a big message in itself. It was disappointing, obviously, that some patients were not able to maintain the weight loss, but then we knew that was going to be a huge problem. They're living in the same world that they started off in. And as I say, they haven't taken this disease as seriously as we might take a cancer and they have not made the permanent changes that we would love them to have made. However, 36% of the entire intervention group remained free from diabetes for two years.

**Jim Hill:** It sounds like being off the medications was a very powerful motivation for these people to help maintain their weight loss. And we talk about that all the time, that motivation is a key in long-term weight management.

**Holly Wyatt:** I think the other thing to realize for the listener especially is it is keeping the weight off that allowed the remission of the diabetes, that allowed them to stay off the medications. It was the weight loss and then keeping it off was the important piece. Because so many times people think, oh, I'm just going to lose the weight, going to get rid of my diabetes. Well, you got to maintain it to be able to continue down that path.

**Mike Lean:** Exactly right, Holly. And I would say that applies equally to prevention of diabetes. So there have been plenty of studies that have shown that people can, if they have pre-diabetes, they're on the slippery slope, if they lose weight, they can prevent the onset of diabetes, but they have to maintain that weight loss. And one of the difficulties here is that so many of our patients are starting off with a body mass index of 32, 35. Then miles over what we used to consider an ideal running race or tennis playing weight, which would be compatible with our evolution as a species. We didn't see people with a BMI of 25 or 30 or 35. And it's no small wonder that as age, as people grow older, that things start to go wrong. And with age anyway, there is a redistribution of body fat. This has been known for some time that whatever your start is, when you get older, you tend to put a bit more fat into your liver, gain a bit of waist as the fat redistributes. And I think probably what we're now saying is that as people lose weight, get clear of their diabetes, they have to maintain that weight loss, as you've said, but probably, and I believe that they will have to lose weight again if they still have a body mass index above something bad. Now, that point at which is bad varies hugely between individuals. So our Asian people, and we did another study after DiRECT, we did a study in South Asian people who had a starting body mass index of only 28, 29. And what we found there was that they didn't have to lose so much weight to get a remission of their disease. They only had to lose eight kilograms, whereas in Europeans, it was over 10 kilograms. But it's likely that because of their genetic difference that they will tend to reaccumulate fat in the liver fat in the pancreas and a big waste if they tend to put on weight so they're in a slightly more precarious position if you like.

**Jim Hill:** Mike you talked about how type 2 diabetes is a progressive disease and it's important to look at treatment early on. Well, let's get back to pre-diabetes because probably a lot of our listeners are in that pre-diabetes range. Much of America's in that pre-diabetes range. It seems like there's a wonderful opportunity where we may be more successful in treating people before they actually get diabetes if we get serious about treating pre-diabetes. And most of the people with pre-diabetes are overweight as well. What do you think?

**Mike Lean:** Yeah, I mean, the whole diagnostic sort of cutoff where we say you have diabetes or you don't have diabetes is arbitrary. We put a line down there with a hemoglobin A1c of 6.5% in America or 48% in the rest of the world. And we say, if you're above that, you have diabetes. And that triggers a whole series of clinical decisions and guidelines. Whereas before below that, the next step down is considered pre-diabetes and the same test is used but it just gives a value which is not yet in the diabetes range. What we know about pre-diabetes is most people with pre-diabetes unless they do something will go on to develop diabetes in time and also this is a disease. This is still the same disease process. The disease we call obesity, which is fat accumulation.

Those people are already putting fat into their heart, into their liver, into other organs which are doing damage at the same time. And they do have increased risks of heart disease. So there's an imperative to treat it. And we have not been treating it up until very recently. So I think America has led the way in this, in going out to identify and propose treatment for prediabetes. In a sense, we probably should put our diagnostic line, which triggers active, aggressive weight management, down at a much lower level now. So that when the hemoglobin A1c registers as prediabetes, I would argue strongly, I agree with you on this, that you would then be able to check that disease process at an earlier stage and get greater clinical benefit. There's a sort of caveat here. The caveat here that is at the moment if you're told we've just done a test and it shows you have diabetes that rings a huge bell for some people who say ah i don't want this disease I'll do something about it. If you're told you have pre-diabetes why is it not for my patients anyway so well I'll…

**Jim Hill:** Deal with it if it happens, yes.

**Mike Lean:** Absolutely. That is the wrong thing.

**Jim Hill:** And the other thing that's a little bit disconcerting is there's a big effort to sort of use medication treatment for pre-diabetes rather than lifestyle.

**Mike Lean:** Yes, of course, the drug industry would jump on that, and they have big time. I'm not going to say they shouldn't. Some of the modern GLP-1 agonist drugs potentially can prevent a lot of people from going on to develop diabetes. But I think if we were to put a little bit of effort into dietary interventions at that stage, you don't have to lose so much weight. You do have to maintain the weight loss to keep the diabetes and the other complications away. So I think the jury is slightly out on this. And I think we've been sort of rushed into or being rushed into prescribing medication at a point when dietary modification brings multiple benefits. So the drugs which are used to treat pre-diabetes include things like metformin. Metformin does have a small benefit. The biggest effect is diet and lifestyle.

**Holly Wyatt:** So this kind of leads to another question. Does it matter how you lose the weight? So you talked about 30 pounds. You lost it with a dietary intervention that you described. Is that important? Or if you get 30 pounds off by another method or even by using a medication now that we have, is that going to do the same thing?

**Mike Lean:** Yes, it will in principle. I mean, I saw a patient in my clinic this afternoon who was a lovely man in his 50s who actually has heart failure and prediabetes. And he got the warning from our cardiologists who are on the ball in Glasgow, and they're recognizing that heart failure is aggravated and even caused by being overweight, by being substantially overweight. He was told, to get ahead and do this, but go and see Professor Lean, because he'll keep you right. This man arrived in my clinic today. He had gone down the road. He'd done what he thought was sensible. He'd lost 18 kilograms in weight. His heart failure had got better. He no longer has prediabetes. And this is a changed man who did it himself. And I think we've underestimated the willingness and ability of many people, not everybody, but many people to lose the weight by whatever means they themselves are comfortable with. Now, as a caveat here, I know there are patients who will use inappropriate diets and I have myself seen patients who've gone on to extreme low-carb diets and ended up with clinical beriberi. Clinical beriberi is a killing disease and luckily... I was able to rescue a couple of patients who would otherwise have died. This is a disease caused by thiamine deficiency because of an extreme low-carb diet with no cereal foods, which is where you get your thiamine from. So it does need to be a nutritionally sensible diet, but there's a big range of nutritionally sensible diets that people can follow. And I think what we need is clear guidance as to what is nutritionally wise, sensible, and safe to help people who want to do it themselves, to do it themselves.

Then the next stage is to use a more formal diet program. And we have diet programs which can be downloaded and be followed online. We have diet programs which can be supported professionally. And that includes the program we use in the DiRECT trial, which is called Counterweight. The Counterweight program we developed in Scotland, there's nothing terribly fancy about it. But the important thing is it was based on behavioral change theory, on a very sound support program, which has continued for as long as you want it, but one year, two years at least. And that is supported by a professional person. And we twigged. There are a few good things that came out of COVID. I probably shouldn't dwell on this too long. But one of the good things that came out of COVID was the recognition that we could use telephones to talk to our patients. Because up until that point, most doctors didn't. You felt you had to see the patient face to face.

Obesity is a funny disease. Patients don't like to be dragged into a clinic, an obesity clinic, and scrutinized and made to go in through this door which says obesity clinic. Telephoning them and saying, right, we're going to deliver this program remotely or by using Zoom or by using WhatsApp has been incredibly effective. And it's been much more inclusive so people don't feel discriminated against. And that we've been able to do as well. So whatever program you use, provided you get the weight loss, it will be effective and they've been good weight losses with some of the low-carb diet programs not the extreme low-carb diet programs some of them they've been good weight losses with high-carb diet programs they've been good weight losses with mediterranean diet programs with the formula diets which in our hands were preferred by our patients because they're secure, because they felt they wouldn't be tempted.

And I think using a food-based program, many people do find temptation a problem. Using a formula diet removes them from any decision-making for a period of 8, 10, 12 weeks, and allows them then to lose the weight confidently, but they then have to be coached into returning to normal foods, or my normal foods, not their old normal foods. So any diet…you mentioned the GLP-1 agonist, the modern drugs, Holly. That's an interesting one because we now know for sure that these drugs together, and don't forget all the clinical trials have used a good diet program alongside semaglutide, tirzepatide. They've all had good dietary advice. And that combination is getting weight losses reliably of about 15 kilograms and about 20 kilograms in some of the studies now. So that is clearly going to be a way to get the weight loss. Of course, these drugs are also treating diabetes. So to be able to be sure you have a remission of the diabetes, you then have to do a therapeutic trial of withdrawing the medication afterwards. That means at a certain point, the patient will say, right, my weight's down and the hemoglobin A1C is down. Let's see if we can now withdraw the treatment and not regain weight and remain in remission to be sure that you have a remission of the disease. So that's a slightly more complicated situation.

And we've shown in Glasgow that using a formal weight maintenance program, the same one that we used in the DiRECT trial, we were able to take people off semaglutide. After two years, they'd lost an average of 17 kilograms, stopped the medication, and they did not regain weight. So having a diet program, a well-designed, supported diet program is able to maintain the weight loss when you stop semaglutide. One of the problems is that the pharmaceutical companies have not actually invested in good dietary research to see how to help people stop the medication. And I think they naively imagined people would just carry on taking semaglutide tirzepatide forever. In fact, my patients, and I don't think they're unusual, after two years, three years, there comes a point when they say, I've had enough of this and I want to stop it. And they do, even if they've been very successful. Now, my own patients, I'm able then to say, okay, we have a diet program, don't regain the weight and we can help you. But I think most patients who are stopping these very effective drugs are not currently being given good dietary programs. It's not expensive. It's not difficult to do this. But a good diet program using sensible foods, using a disciplined way of eating, they've already lost the weight. They know how it feels to have lost the weight, and their quality of life has improved. So they're actually quite inclined to do it.

**Jim Hill:** Well, we agree with you there. One quick question. You haven't mentioned my favorite E-word, exercise. What's the role of physical activity and exercise in your programs?

**Mike Lean:** Oh, Jim, as you know, exercise makes you feel great. And those people who are a lot of people with weight problems have been treated for depression. Very often, I don't think they actually have depression, but they're a bit unhappy or very unhappy. And physical activity is one of the things that really does improve well-being and quality of life and mood. So there's that big plus feature. In terms of the weight loss, the evidence says that exercise can contribute to helping with weight loss, particularly in young men, but not so much in other subgroups. It can't do the job of diet restriction. It simply can't. It doesn't have the muscle, if you like, to get the weight loss that diet restriction has. So the combination together is good if people can do it. I'm dealing with a lot of patients whose body mass index is above 30. If they try to take more exercise, they do damage to their hips, to their knees, and they feel rotten. And added to that, if they have type 2 diabetes, they have fat-infiltrated muscle, which fatigues very easily. They actually suffer if they try to exercise. They're already working hard, shifting 100 kilograms, that's 200 pounds of weight. They're already working flat out. So to try and increase exercise at that point is just not feasible. And it's actually counterproductive. We found that people do better if we say to them, right, get the weight off with diet. That's the big one. The big hit is your diet, diet restriction, get the weight off. Then if you're physically able, then increase physical activity.

**Jim Hill:** Well, we agree with you that exercise doesn't add a lot to weight loss, but I think exercise becomes really critical during weight loss maintenance. We can talk about that a little bit more, but…

**Mike Lean:** You don't want to have an argument today, Jim.

**Jim Hill:** Not that I'd like arguing with Mike. You know, I say that we don't know enough in this field to agree on everything. It's okay to disagree. And we'll save that for another time. But Holly, maybe kind of summarize what we've heard in this segment?

**Holly Wyatt:** I think this, for some people, will be really eye-opening. The idea that if you have prediabetes or you have type 2 diabetes, you can actually reverse it, go into remission, get off your medications, or take less medications. But if you lose weight, and it seems like around, 30 pounds. It depends maybe exactly on the person and how much, but that's a doable amount for a lot of people. I like that you kind of said it's not one way. Getting off the weight, you don't have to, there's not one secret diet or one way to get the weight off, but getting the weight off, the weight loss seems to be important in that reversal. And you talked a lot about where the fat is and why it is. And I think that that's good. And then also though, keeping it off, if you regain the weight, you will then go back to having type 2 diabetes. And so I think it fits really well. And I love that you make this important. You know, you compare it. This is an important thing. It's not just something that would be nice to have. This, you don't want to have type 2 diabetes. And we need to be thinking about it differently, perhaps, in terms of the seriousness of it. What else, Jim? What did I miss?

**Jim Hill:** Oh, I think you hit it. I think you hit it. And it really is, again, I would point out, that being able to go off your diabetes medication is probably one powerful source of motivation for people who work to keep the weight off. And you do have to keep the weight off. It's not just losing it. It's keeping it off.

**Mike Lean:** I think, can I add to that? Getting off medication is really important, but it's also very important medically to keep a check that people when they stop it, don't get into trouble. And there is a small proportion of people who, it's very small, perhaps 5%, whose diabetes, in retrospect, is not caused by the excess weight. They may be overweight and heavy, and they try to lose weight if they have damage to the pancreas for another reason. And that can include a history of pancreatitis. You know, we've had patients who, when we go back into their history, we find they had recurrent abdominal pain years ago, and it was pancreatitis. And that has actually limited their pancreas so that they do depend on medication. There are a few people like that.

**Jim Hill:** So one final question for you, Mike. You have done a study which has gained a lot of recognition. People all over the world recognize this. How confident are you that we're actually going to change how we approach type 2 diabetes and that we're really going to get serious about lifestyle approaches?

**Mike Lean:** Well, I'm 100% confident, Jim. We've already got guidelines. The European guidelines have put remission of diabetes as top priority at the time of diagnosis. Don't delay, get a remission as fast as possible. And we're taking this forward now with a view to nudging governments into putting more effort into prevention of this disease because that's really where the big effort goes.

And I have now a very nice project, which is funded, running in Nepal, where we're doing the whole thing with very simple traditional foods, not using any formula diets, not even using doctors or nurses, but using community workers and traditional foods. Provided we can identify people who either have diabetes or pre-diabetes, then getting to lose quite a modest amount of weight is enough to kick that disease out. So I think we're going to see this one study completed five years ago now has now spawned oh to my knowledge about 10 or 15 similar and bigger studies worldwide and I've been involved with some of them it's also now kicking into guidelines around the world. It's also now nudging our politicians to the point where perhaps they will actually do something about checking the profusion and the unlimited marketing of foods which are causing the weight gain in the first place. And that's going to come, I think, the big push is going to come from people who either have or have family members with diabetes. They are the ones whose voices need to be heard.

**Jim Hill:** So another good reason to get serious about the weight loss. Mike, thanks so much for giving your time today. And we will talk to you next time on Weight Loss And. Thanks, everybody.

**Mike Lean:** Cheerio, Jim. Cheerio, Holly. Thanks very much.

**Holly Wyatt:** Bye, everybody.

**Jim Hill:** And that's a wrap for today's episode of Weight Loss And… we hope you enjoy diving into the world of weight loss with us.

**Holly Wyatt:** If you want to stay connected and continue exploring the “Ands” of weight loss, be sure to follow our podcast on your favorite platform.

**Jim Hill:** We'd also love to hear from you. Share your thoughts, questions, or topic suggestions by reaching out at [weightlossand.com](http://weightlossand.com/). Your feedback helps us tailor future episodes to your needs.

**Holly Wyatt:** And remember, the journey doesn't end here. Keep applying the knowledge and strategies you've learned and embrace the power of the “And” in your own weight loss journey.