David Jones

Mounjaro is the most powerful weight-loss jab currently available – but it may soon be toppled by ‘Godzilla’ drug retatrutide and other emerging injections, a study suggests.

Researchers found tirzepatide – the active ingredient in the blockbuster drug dubbed the ‘King Kong’ of weight-loss jabs – can see patients shed more than a fifth of their body weight after around 17 months.

But retatrutide, nicknamed ‘Godzilla’ because it is hoped to be even more powerful, can see patients lose almost a quarter of their weight after just 48 weeks.

Known as ‘Reta’, the experimental jab has yet to be approved for widespread use, although it was given the green light in the US last month for select patients with an urgent need.

Another experimental jab, amycretin, produced almost the exact same level of weight loss as retatrutide after just 36 weeks.

This suggests the drugs could become the most potent weight-loss jabs ever developed if they get the green light from health officials.

By comparison, semaglutide injections such as Wegovy and Ozempic can trigger weight loss of up to 18.7 per cent over a similar period.

Mounjaro also appears to produce greater weight loss than the new once-daily tablet treatments recently approved in the UK – the Wegovy pill and Foundayo.

Mounjaro is the most powerful fat jab currently available – but it may soon be toppled by other emerging treatments, a study suggests

The Wegovy pill can see patients lose as much as 15.5 per cent of their body weight after 68 weeks, the study showed.

Meanwhile Foundayo, also known as orforglipron, can see patients lose up to 14.7 per cent – though this is after just 36 weeks.

Researchers launched a new so-called systematic review of the drugs, known as GLP-1s, after carrying out a similar analysis last year.

They analysed 38 trials with more than 25,000 participants to study the safety and efficacy of the treatments compared with placebo medicines.

This included looking at new, experimental drugs which are yet to be approved, including retatrutide and amycretin.

The increasing potency of the drugs is thought to be partly down to the number of different hormones they mimic in the body.

Semaglutide, the drug behind Wegovy and Ozempic, mimics a gut hormone called GLP-1, which helps people feel fuller for longer and reduces appetite.

Tirzepatide – the drug in Mounjaro – went one step further by mimicking both GLP-1 and another hormone called GIP, which is also involved in regulating appetite and blood sugar. 

Experts believe targeting the two pathways together is one reason it can produce greater weight loss than semaglutide.

Retatrutide goes further still. Known as a ‘triple agonist’, it targets GLP-1 and GIP as well as a third hormone, glucagon.

As well as helping control appetite, glucagon is thought to increase the amount of energy the body burns – potentially explaining why retatrutide has produced even greater weight loss in trials.

Amycretin works differently again. It targets GLP-1 alongside amylin, a hormone released by the pancreas after eating which sends signals to the brain that help people feel full.

The researchers, from McGill University and the Jewish General Hospital in Montreal, Canada, also looked at side effects reported by people using the drugs.

Around 40 per cent of people on placebos in the trials reported gastrointestinal side effects, compared with 76 per cent of those who took the jabs or pills.

These have long been known as the most common side effects of the drugs and include diarrhoea, vomiting, nausea and constipation.

Around 10 per cent of people had to stop taking the drugs as a result.

There were also rare reports of severe biliary disorders, which typically include gallstones, as well as pancreatitis, psychiatric disorders and six deaths.

The researchers, whose findings were published in the Annals of Internal Medicine journal, noted that the trials for each of the drugs differed, meaning the results cannot be directly compared.

The findings relating to the drugs’ side effects also come after official drug safety figures separately showed 216 deaths in the UK have been linked to the jabs.

Earlier this month, the Daily Mail reported that a total of 150,000 adverse reactions have also been associated with the drugs.

Semaglutide was linked to 59 deaths, meanwhile, liraglutide, known as Saxenda, was associated with 37 fatalities.

The figures were uncovered in so-called Yellow Card reports made to the Medicines and Healthcare products Regulatory Agency.

Officials said that the reports do not prove that a medicine caused a reaction to happen, only that it is suspected by the individual making the report. Other health conditions may have been at play.

Five women waited on the ward, sitting up anxiously, stripped bare to their waist. This was on their surgeon’s orders, to save him time as they were examined by him ahead of their surgery that morning.

He led the way around the beds at The Royal Marsden Hospital with me, a trainee oncologist, bringing up the rear of the team.

This was the reality of breast cancer treatment in the 1970s when I began my career.

Did those women mind? Did they feel embarrassed, sitting half-naked with seven men around their bed? No one ever asked them, as far as I was aware. But even at the time it felt awkward to me. Such a practice would be inconceivable nowadays. And it’s not the only thing that’s changed.

In the 1970s, most women who developed breast cancer died of it – at least 60 per cent. Today, most women are cured; fewer than 30 per cent die.

I’ve changed too. Today, 50 years on, I am no longer the junior at the back – I became, until recently, a professor of cancer medicine at The Institute of Cancer Research, as well as being head of the breast unit at The Royal Marsden Hospital, in London. I’ve conducted international trials into treatments for breast cancer, among them research into the use of the drug Herceptin for early breast cancer.

And, of course, I’ve cared for many thousands of women.

Through treating them, I’ve learnt so much, which I want to share with you – with the wish this insight might give you hope if you or someone you love is diagnosed with breast cancer. For there are many reasons to be hopeful. The future is much brighter for those who have breast cancer than it was…

The future is much brighter for those who have breast cancer than it was, writes Professor Ian E Smith. Today, most women are cured; fewer than 30 per cent die

Why chemotherapy isn’t always right

Not long after I became a consultant around 1980, I treated a gentle middle-aged woman called Mrs Baker. It’s no understatement to say she changed my professional life.

Three years after her original breast cancer diagnosis, she developed secondary cancer in her liver, for which there is no cure.

Of course, this is very serious. But you can live with metastases in the liver, sometimes for many years, without any significant symptoms, provided the disease is controlled with treatment.

I started Mrs Baker on chemotherapy. The cancer on her liver did regress but she found the side-effects – nausea and exhaustion – very hard.

Each month, I cajoled her to have another course; each month, she reluctantly agreed.

Then, one day, the clinic nurse came to me and said: ‘Look at this.’ She had found in her notes a photo of Mrs Baker before her treatment, smiling, looking well.

Six months later, she was almost unrecognisable, her face thin and drawn, with an ill-fitting wig as a result of hair loss – and, most heart-rending of all, an expression of pure misery.

I was shocked. She had trusted me, and I had done that to her. This was a perfect example of a treatment being worse than the disease.

This would have been bad enough if it had been the only option – but it wasn’t. Hormone-blocking drugs, given in tablet form, also cause cancers to shrink, sometimes for a long time, years rather than months, without the toxic side-effects of chemotherapy.

I could – and should – have simply given her hormone-blockers, with a good chance she could have lived a few more years of quality life before needing to turn to chemotherapy.

I saw, painfully clearly, that I had been very wrong.

Mrs Baker led me to question whether chemotherapy was necessarily the best first option.

Since then, I’ve tended to be much more conservative in its use, both in early and advanced breast cancer.

Indeed, trials have since confirmed that for patients with advanced breast cancer that is oestrogen-receptor positive (ie they grow in response to the hormone oestrogen), the best treatment is generally hormone-blocking tablets first, and often second, too.

Chemotherapy should be reserved until tumour resistance to hormone therapy has developed.

Despite this, there’s still an instinctive belief amongst some of my colleagues that if a patient is young, or if they have disease in the liver, for example, then it’s better to give chemotherapy first, ‘because it’s more likely to work’ or ‘because it works faster’.

Neither of these dogmas is backed up by convincing data.

Don’t get me wrong. Chemotherapy used in the right context can relieve symptoms, improve quality of life when the patient is feeling very ill from cancer, and undoubtedly saves lives.

But ‘the right context’ is key. Far too often, chemotherapy is used too early and in too large a dose, and in patients with advanced breast cancer, when other options – including, sometimes, a simple ‘watch’ policy – are more appropriate.

In my view, we could sometimes try a smaller dose of chemotherapy than the maximum permitted level or duration. We don’t have strong evidence this would be detrimental to outcome, so why not use less when we know a moderate reduction in dose can lead to a marked reduction in side-effects and toxicity, with a better quality of life?

Some younger cancer specialists seem more enthusiastic about chemotherapy’s widespread use than older specialists. It seems to me a failure on my part, and of my contemporaries, not to have argued for greater caution more strongly.

And yet concurrently interest is now starting to grow in designing less intensive and much less toxic chemotherapy treatments. This has been a long time coming.

The reality is cancer treatment doesn’t always need to be torturous to work.

When to tell a patient their life expectancy

Fran’s story, however, shows the power of chemo – and of hope.

Aged 26, Fran, a personal trainer, had breast cancer for which she had surgery. She was later discovered to have a brain tumour. After this was removed, a cancer specialist told her: ‘I’m afraid this cancer doesn’t look good’ and that there were bound to be residual cancer cells in her body.

A scanning electron micrograph of a breast cancer cell. Trials have confirmed that for patients with advanced breast cancer that is oestrogen-receptor positive, the best treatment is generally hormone-blocking tablets first, and often second, too

They said she had two years to live and all she could be given was palliative treatment. All hope had been taken from her, but she sought a second opinion and found her way to me.

I saw immediately she wasn’t going to give in without a big fight.

The most important question in my mind was whether Fran really was incurable beyond doubt – in that case, palliative treatment with low toxicity was the best and kindest approach – or whether there was the slightest hope.

If the latter, treatment would involve chemotherapy for months and specialised radiotherapy to the brain to try to mop up any lingering cancer cells.

In general, brain metastases in breast cancer are not good news. But Fran only had one, rather than the usual multiple metastases. This had also been present right from her original diagnosis – highly uncommon.

So I thought, why not be optimistic and go for a cure, particularly in someone with so much life left to fight for?

Today, over five years on, Fran has celebrated her 30th birthday, and she takes tamoxifen (a hormone blocker). She’s still a personal trainer, now working with cancer patients.

I have real reservations about telling a fit and well patient such as Fran they have only two years left to live.

If a patient is dying and has only a few weeks left, then of course they need to know. But giving someone like Fran a specific life expectancy, be it two years or six months, takes away hope.

And one thing I have truly learned in my long career is hope is what keeps many people going.

I’m not advocating dishonesty, but it is possible to give an accurate picture without taking away all hope – the one thing that might help to get them through the many months, or even years, of treatment ahead.

This is particularly true for advanced breast cancer, which is very unpredictable, but patients can sometimes live for many years.

If they can remain well for a while, a new drug may turn up, as has happened with several of my patients.

But if you give a specific time limit, the patient will hold on to that number and then the hope is gone.

Women who can now avoid surgery

One of the most significant developments in understanding breast cancer has been the realisation it’s not one disease with a one-size-fits-all approach.

Instead, it consists of several different subtypes, each behaving in its own way, and each needing its own treatments.

Nowhere is this more evident than in the field of preoperative chemotherapy, where chemo is given before surgery.

The cancer subtype called HER2-positive (which grows in response to the HER2 protein produced naturally in the body) is particularly responsive to this approach. A combination of anti-HER2 drugs, including Herceptin, and chemotherapy usually causes very marked shrinkage of the cancer.

Indeed, in around half of patients the cancer disappears completely, and they have a very good long-term outlook.

This raises an intriguing possibility. Do patients with HER2-positive breast cancer whose cancers disappear completely need surgery – which can range from excision of the tumour bed to complete mastectomies – at all?

You might call this question the final frontier for breast cancer.

We don’t have a definitive answer yet, but no surgery is gradually becoming an option at The Royal Marsden – and in a few other cancer centres for these particular patients.

And, so far, results are very encouraging, with no one in our own experience having had a relapse. One patient of mine had treatment without any surgery 12 years ago, without a recurrence. These patients are, however, still having radiotherapy as a precaution. But there is a question about whether even this is necessary.

This has so far never been tested formally, but let me tell you about a patient I shall call Jean. She was in her early 90s when I first met her, but still very fit. She loved open air and long walks. She had a lump which was a fairly large HER2-positive breast cancer. Her husband of many decades was dying of a different cancer and she was unenthusiastic about any treatment.

I persuaded her to try Herceptin, along with as gentle a form of chemotherapy as I could devise, using only one drug and in a small dose.

After three shots of this, her cancer had shrunk dramatically.

At this point, she gently, but firmly, declined any more chemotherapy, but she agreed to continue Herceptin.

She remained adamant she didn’t want surgery – or radiotherapy. I had to tell her this was risky but secretly, I was on her side; she was sharp and completely understood the issues.

Professor Ian E Smith is a world-renowned breast cancer specialist. He’s conducted international trials into treatments for breast cancer, among them research into the use of the drug Herceptin for early breast cancer

Each time I saw her, I expected to find the lump had reappeared. Eight years have passed and so far this hasn’t happened.

Her life remains full and happy. Although nothing is certain in breast cancer, her particular subtype is one that usually recurs within five years, or not at all.

It seems to me Jean is, so far, one of the very few patients anywhere whose breast cancer has been cured by drugs alone.

I use ‘so far’ deliberately; I hope and believe she’s the forerunner of many more patients, as our treatments and our experience develop in this new area.

The Holy Grail: curing secondary cancer

I’ve always hoped to one day start curing secondary breast cancer – which is usually incurable, albeit sometimes proving fatal only after many years. The frustrating reality is this hasn’t happened.

But there is a promising area of research being pioneered by one of my close colleagues at the Marsden, Professor Nick Turner, who is beginning to change the way we monitor breast cancer patients through the use of liquid biopsies – these detect tiny parts of the cancer cell DNA in the blood left behind after initial treatments.

Potentially, Professor Turner’s technology allows us to kill off these tiny cells before there are too many and they trigger another tumour.

Liquid biopsies also reveal the mutations of that particular cancer cell, potentially giving us clues as to what treatments might work for that individual patient.

Another big advantage is that this cancer cell DNA (or ctDNA) can be detected with a simple blood test, in contrast to secondaries in the internal organs, including liver, lung and bone, that require special needle biopsies under imaging guidance – an uncomfortable experience for the patient, and potentially a risky one, too. This also means ctDNA samples can be taken regularly during treatment to monitor whether the therapy is working.

The big problem up until now has been that we don’t know which patients will relapse. Now a major trial called TRAK-ER, led by Professor Turner and currently under way in multiple hospitals in the UK and France, is looking to identify patients at risk of relapse, by regular blood tests to detect the presence of ctDNA for early signs of recurrence before it appears on scans. It involves patients who have ER-positive breast cancer, found in around 70 per cent of patients.

Most patients with this subtype are cured with surgery and hormone tablets, but around 20 per cent will relapse over the next 20 years. The trial is currently running well and we hope it will pave the way for regular ctDNA analysis to become a routine approach.

Truth about the cancer risks of HRT and wine

One of the most common questions patients ask is: ‘Why did I get this?’ They are anxious that they’ve done something wrong. Usually, though, most patients are just unlucky.

Nevertheless, some recognised factors – such as ageing or obesity – might put a woman at increased risk.

But I feel some factors are overblown, for instance, HRT. Notoriously, the 2002 Women’s Health Initiative trial found an increased risk of 25 per cent for breast cancer after using HRT and certainly this caused a lot of worry. But this refers to the relative increase compared with women not taking HRT.

Over the trial’s five years, there were four extra cases of breast cancer for every 1,000 women taking HRT, an additional 0.4 per cent. Not exactly a big risk.

This reminds me of a patient, a doctor herself, who I recently met by chance 20 years after seeing her to discuss HRT.

Menopausal symptoms had been ruining her life, and she was considering early retirement; she’d been told under no circumstances should she take HRT.

I told her the risk, even for women who’d had breast cancer like her, was small – and showed her published data confirming this. I thought she should start HRT – and she did. Since then, she has gone on to become a figure at the top of her profession. ‘You changed my life,’ she said, simply. ‘Thank you.’

While there’s also evidence alcohol increases the risk of breast cancer, the figures again refer to relative risk, so could sound more alarming than they are.

Around one in seven women in the UK are going to get breast cancer – around 14 per cent of all women. One drink per day is going to increase that by around 10 per cent of the 14 per cent – ie, the woman’s risk would be 1.4 per cent greater than a woman who didn’t drink this amount.

Some may feel this is enough to avoid alcohol. Personally, I sometimes feel the anti-alcohol argument is overdone, and women who enjoy a glass of wine might conclude a one or two in 100 extra risk is worth taking when balanced against the pleasure of a drink.

Adapted from Doctor, I’ve Found A Lump by Professor Ian E Smith (DK Red, £20), to be published September 10. © Ian E Smith 2026. To order a copy for £18 (offer valid to 15/09/26; UK P&P free on orders over £25) go to mailshop.co.uk/books or call 020 3176 2937.