New risks associated with weight loss jabs

The weight-loss jab Mounjaro is being made available at GP clinics in England – but only for those who meet strict criteria. The weekly injection, which can help people lose up to 20% of their body weight, is already in high demand globally. But doctors warn supplies are limited, the drug is costly, and side effects like nausea and vomiting are common. There are also concerns it may interfere with how well the contraceptive pill works, and even rare cases of inflammation of the pancreas have been reported. I've been speaking with John Wilding, who leads clinical research into obesity, diabetes and endocrinology at the University of Liverpool…

John - So Mounjaro, which is also known by the name Tazepatide, is given by injection once a week. And the way it works is by mimicking two of the body's natural hormones that tell us after we've eaten a meal that our stomach is full and that we've had enough to eat. So these are hormones that are naturally released from the gut to tell us we're full. They also do other things like stimulate insulin secretion, which is why they've been used to treat people with type 2 diabetes. But it's the effects on the brain and on appetite control that are the reason why they're effective weight loss medications.

Chris - When people take them, they lose between 10 and 20 percent over time of their body weight. Why do they lose that? Is it just that they don't feel hungry so they eat less? Or do they eat less of the wrong things? Or is it a combination of those things? What do the trials look like?

John - That's a really interesting question. As you rightly point out, at the highest dose we see on average people lose about 20 percent of their body weight. What they're doing is partly mimicking these natural hormones so you feel fuller after you've eaten. The example that I often use is you eat a sandwich and you feel like you've had Christmas dinner. So it's more about making you feel full rather than making you feel less hungry. Although they do probably also help people to feel a bit less hungry as well. In terms of what people choose to eat, some people do tell us that they tend to crave less sweet foods and fatty foods and unhealthy foods when they're taking these medicines. But that evidence isn't really very strong at the moment.

Chris - Is there any evidence people also over time change their eating behaviour in the sense that when a person has had a course of this they reach closer to their ideal body weight? Do they then maintain that when they stop? Or are you condemned effectively to enriching the share price of the company that makes these drugs indefinitely in order to keep the weight off?

John - That's a really good question. The way I would frame this as a clinician who treats people with severe obesity and weight-related complications is firstly to say that of course as you lose weight eventually you will reach a plateau. Everybody will stop losing weight. Usually after about a year you reach a new steady weight while you're taking the medicine. If you stop the medicine then of course it stops working and at that point people tend to gradually put weight on again. Of course some people will be able to maintain the weight loss long-term. That's relatively uncommon. Most people would put the weight back on once they stop it. So we do need to think about these drugs much in the same way as we think about drugs for other long-term conditions like diabetes or hypertension or high cholesterol as treatments that people take long-term.

There is ongoing research that is asking the question whether it might be possible once you've reached that point of weight where you want to be whether you might be able to maintain the weight at a lower dose which would obviously be a good thing but we don't know whether that is the case yet.

Chris - What about the side effects? We've spoken to people who've taken these drugs. Sometimes they found that they had to stop taking them because they just couldn't handle those side effects. There isn't a free lunch with any drug, is there? There are always potentially side effects. What does the side effect profile for these agents look like?

John - You're absolutely right. Of course all medicines have side effects but what I would say is the most important side effect that everybody needs to know about is the fact that these drugs when you first start taking them particularly or when you increase the dose tend to cause nausea. Most of the time what we find is that if we increase the dose gradually that allows us to find the right dose that most people can tolerate.

Chris - And the impact on contraception? Because that's emerged more recently and I know a lot of GPs have expressed considerable alarm about that.

John - So in fact we've been using these medicines to treat diabetes for many years and as with all medicines when they're first developed we are very very careful in the clinical trials not to include women who might become pregnant because we don't know the long-term effects on a growing baby in the womb. So there is very little clinical data about the safety in pregnancy. There is a very specific issue with Tazepatide with Mounjaro which is as with all of these drugs it slows down the emptying of the stomach. So in one small study that was done in women taking oral contraceptives what we found was that it slows the absorption of the contraceptive and therefore that might potentially reduce the effectiveness of the contraceptive.

Chris - What does the economic argument look like? Because you've got politicians saying they want to do this on potentially a massive scale relatively speaking across a whole country in primary care so this would be family doctors who are able to administer these agents. Does this look like it makes for good value for money? Because they're not cheap these drugs.

John - So one of the jobs of NICE, National Institute for Health and Clinical Excellence is to actually look at not just the effectiveness of medicines but about the cost-effectiveness of medicines. And the NICE technology appraisal for Tazepatide has come to the conclusion that these medicines are cost-effective for use in the NHS and that is done for most medicines that we use in the NHS and this medicine comes into the same sort of range as many other treatments that we use in terms of its cost-effectiveness. One thing that the NHS has recognised is that to make that available to everybody who might be eligible immediately would be very expensive. And so what they've done is they've tried to target this at those people who are perhaps most likely to benefit early on. Now we can argue about whether the group that they have chosen is the right group. The rollout in primary care at the moment is only for people who have very severe obesity, a body mass index above 40 and have four out of five named complications from diabetes, heart disease, sleep apnea, high blood pressure and high cholesterol. So you have to have four out of those five and a body mass index above 40 because that's where they think the cost-effectiveness is likely to be greatest. That will gradually relax over time as we gain more experience and GPs become more experienced with prescribing the medicine.

Chris - The thing that I'm finding it hard to wrap my mind around though is that, as you've eloquently told us, this may translate into, say, a 20% reduction in body weight. But some people are 100% or 200% in some cases over their ideal body weight. So they're still going to be extremely overweight despite taking these drugs and running the risk of all the side effects that you've outlined. So is there a vanishing return there?

John - What I would say is that, of course, there are some people who are twice their body weight and if they lose 20% of their overall body weight, that's a substantial amount of the extra weight that they're carrying that they lose and about two-thirds of that weight that they lose will be fatty tissue, which is what we're trying to help reduce with obesity. Yes, of course, it's not going to get everybody to an ideal body weight, but there's no intervention that does that except for perhaps some of the most extreme forms of bariatric surgery that are very, very rarely performed because they have so many side effects. So we're actually, with these medicines, getting quite close to what we see with the more commonly used weight loss operations, like gastric bypass, and these medicines are a little bit less effective, but not that much less effective than these operations now.