They’ve been hailed as a ­medical miracle: GLP-1 drugs – the weight-loss injections sold as Wegovy and Mounjaro – have helped millions shed ­stubborn pounds and have been shown also to cut the risk of heart attack and stroke by around 20 per cent, even ­independently of weight loss. But are the drugs starting to lose their shine, with concerns emerging over their side-effects?

More than 1.6 million adults in ­England, Wales and Scotland used weight-loss drugs such as Wegovy and Mounjaro between early 2024 and early 2025, according to new research published in the journal BMC Medicine.

With the increasing use of these GLP-1 drugs, anecdotal evidence suggests more people are also turning up in A&E with constant vomiting and dehydration and, more recently, complications linked to gall­bladder disease and acute pancreatitis (sudden and potentially life-threatening inflammation of the pancreas).

Indeed, the medicines watchdog, the Medicines and Healthcare products ­Regulatory Agency (MHRA) has just updated its guidance to doctors and patients after a spike in reported fatalities linked to acute pancreatitis.

Under its Yellow Card report scheme (for clinicians and the public to flag suspected side-effects), there were 1,143 reports of acute and chronic pancreatitis, including 19 deaths, in people taking GLP-1s between 2007 and October 2025.

Almost all of these – 973 reports and 17 deaths – were recorded in 2025 alone. Most were linked to tirzepatide (brand name Mounjaro), with 807 reports; and 166 to semaglutide (Ozempic and Wegovy). There were also 146 reports involving liraglutide ­(Saxenda) and 61 for dulaglutide.

Patient leaflets for some GLP-1s, including Mounjaro, already list acute pancreatitis as an ‘uncommon side-effect’ affecting up to one in 100 people. But the MHRA has now updated its own product information to highlight the ‘small risk of severe acute pancreatitis’ in patients taking GLP-1s.

This is not the only worrying development linked to the drugs. The number of ­operations performed by the NHS to remove gallbladders shot up by nearly 15 per cent in the past year – from 69,745 in 2023-24 to 80,196 in 2024/25, figures from NHS England show – something doctors blame on the increased use of GLP-1s.

Professor Ahmed Ahmed, a ­consultant gastrointestinal and ­bariatric surgeon at Imperial College Healthcare Trust in ­London, says the ­timing is no accident.

‘It’s notable because you don’t see that much fluctuation from year to year,’ he says. ‘And I bet you it’ll be even higher next year.’ He notes that ‘nothing else has changed’, pointing to the explosion in use of weight-loss jabs over the past 18 months.

The most common reason for surgery to remove the gallbladder is gallstones (which are usually formed of cholesterol) – these are a ­recognised side-effect of any rapid weight loss.

When weight is lost quickly, the liver releases extra cholesterol into bile (a digestive fluid). At the same time, the gallbladder ­empties less often. This means bile stored there becomes thicker and more likely to form stones.

Gallstones are already listed in GLP-1 leaflets as a common side-effect, affecting up to one in ten people who use the jabs.

What worries doctors is not so much that gallstones occur per se (they don’t always cause problems unless they block a duct in the gallbladder) – but the speed and scale at which complications are now appearing.

(Around 20 per cent of people with gallstones will need gall­bladder removal, according to NHS England – as GLP-1 drives gallstones, the assumption is that more people will develop pain and need surgery.)

Professor Ahmed says the rise in gallstones because of GLP-1 use is also linked to a rise in cases of pancreatitis being reported.

If stones slip out of the gall­bladder and block the pancreatic duct, they can trigger acute ­pancreatitis – this happens in around 3 to 7 per cent of people who develop gallstones. GLP-1 drugs may also have a direct effect on the pancreas itself, independent of weight loss, he adds.

Separately a number of patients in the US have now filed lawsuits against GLP-1 drug manufacturers claiming they were harmed by severe side-effects they weren’t warned about, including vision loss. UK law firms report they have also been contacted about similar complaints. But why are these more serious effects ­apparently emerging now?

What’s happening isn’t without precedent – these reports about GLP-1s follow a familiar pattern seen with past blockbuster drugs, with problems sometimes only emerging once millions of people start using them longer term.

Vioxx was celebrated as a revolutionary painkiller that was easier on the stomach than traditional non-steroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen) when it was approved in 1999 in the US. However, as it became more widely prescribed, reports emerged showing it significantly increased the risk of heart attacks and strokes. The drug was pulled from the market in 2004, by which time an estimated 80 million ­people worldwide had taken it.

Sarah Jackson, a professor of behavioural science and health at University College London, says: ‘Clinical trials are designed to show whether a drug works and to catch common side-effects, but they’re relatively small and tightly controlled.’

With Mounjaro – now taken by millions – around 4,800 patients were included in the major trials.

‘Much rarer harms won’t emerge until a drug is used more widely,’ adds Professor Jackson.

When drugs hit the real world, a broader range of patients start taking them – people with different underlying conditions, genetic dispositions (that affect how they metabolise drugs) or already ­taking other medications.

Or they’re using the drugs in ways not tested in trials which ‘may lead to a different side-effect profile’, says Professor Munir ­Pirmohamed, chair of the ­Commission on Human Medicines and a consultant physician at Royal Liverpool University Hospital.

Just five years ago, GLP-1s were barely in the public eye (Wegovy and Mounjaro for weight loss only launched in the UK in 2023). As the uptake of the drugs has been so rapid, doctors worry that ­people are now rushing to take them without properly understanding the risks involved.

And drugs surveillance systems are racing to keep up. For the MHRA, the popularity of GLP-1 drugs has triggered a rare move. Rather than relying on routine safety alerts via its Yellow Card scheme, it has issued dedicated, stand-alone guidance on the drugs, which will be revised as new risks are identified.

Last week, it issued a patient safety alert, warning that semaglutide may, in very rare cases, cause sudden vision loss.

It said the risk of the eye condition, non-arteritic anterior ischemic optic neuropathy (NAION) appears small, affecting up to one in 10,000 users, but urged patients to seek urgent medical help if their sight changes suddenly.

The precise mechanism remains unclear, but it’s thought semaglutide’s rapid effects on blood sugar, blood pressure and body weight may affect blood flow to the optic nerve.

A study published in the journal JAMA Ophthalmology in 2024 found that patients with type 2 diabetes taking semaglutide had more than four times the risk of developing NAION compared to those on other diabetes drugs. For overweight patients, the risk was more than seven-fold.

‘This is one of the most worrisome side-effects associated with the GLP-1 class of drugs,’ says Cameron Stephenson, a lawyer with Levin Law, one of several US firms ­handling litigation involving more than 3,000 lawsuits against GLP-1 manufacturers. ‘For the most part, it’s permanent vision loss and is obviously devastating.’

He adds that many of the patients in the lawsuits ‘also suffer from ­gastroparesis or some form of bowel obstruction’, conditions that ‘can require hospital treatment and even surgery’. The plaintiffs ‘allege that GLP-1 drug manufacturers were aware or reasonably should have been aware of the gastrointestinal problems and NAION side-effects and failed to adequately warn of these conditions. The labels for all of these drugs still do not adequately warn patients and healthcare ­providers of these conditions’.

Sarah Moore, a partner at London-­based legal firm Leigh Day, says they have been contacted by a number of people who believe they developed NAION after taking Mounjaro and claim the product information only indicates blurry vision but not sight loss.

Whether or not warnings to patients were adequate will likely be a point courts have to decide in future. ‘The jury’s out on whether it’s a true link,’ is the view of Mike Burdon, a ­consultant ophthalmologist at Queen Elizabeth Hospital Birmingham.

He points to a major study published in the American Journal of Ophthalmology in 2025, involving around 120,000 patients, which found no evidence that people taking semaglutide or other GLP-1 drugs were more likely to develop NAION than similar patients who were not on them.

Even if there is an association, NAION is rare – affecting perhaps ten in 100,000 people aged over 50 annually, he says. He adds: ‘If you compare it with the good that the drug is doing in terms of treating diabetes, reducing weight, reducing the risk of hypertension and diabetic complications, you would say that the overall benefit on the whole outweighs any potential side-effect.’

But what complicates this argument is that the boom in GLP-1s use isn’t always being driven by medical need. Research suggests that just a fraction of the 1.6 million people in the UK who have used GLP-1 drugs for weight loss in the past year will have been given them on the NHS. NHS England expects to treat just 220,000 patients through its specialist programme over three years.

Dr Oksana Pyzik, an associate professor of pharmacy practice at University College London, warns that the ‘reliance on self-reported ­medical history, weight, BMI and photographs – all of which are easy to manipulate – combined with ­minimal or no follow-up monitoring, ­creates an unacceptably low bar for access for GLP-1s.

‘While this may be legally permitted, it raises patient safety concerns, particularly for younger individuals who may misreport eligibility or underestimate the risks, influenced by celebrity influencers pushing the products and social media trends.’

Professor Judith Korner, who directs the Metabolic and Weight Control Centre at Columbia University in the US, says: ‘If patients are ordering these online, do they have someone to go to with medical knowledge about these medications in case something happens?’

She warns that people react very differently to these drugs. Some need much lower starting doses, while others develop side-effects – such as severe nausea and vomiting, bowel problems or low blood sugar – that require careful adjustment or stopping treatment altogether. (Doctors say that side-effects are most likely to flare when the doses are increased – which they generally are, incrementally – when the body is still adjusting.)

Concerns are not limited to physical side-effects, with some research suggesting GLP-1 drugs could also affect mental health. This could be a blind spot as people with psychiatric conditions are usually excluded from drug trials, resulting, as leading researcher Professor Yi-Sun Yang, from Chung Shan Medical University in Taiwan, says, ‘in a lack of data for understanding the long-term consequences of GLP-1 drug use’.

In a study he led, published in ­Scientific Reports in 2024, based on eight years of data from more than 160,000 adults with obesity, people taking GLP-1 drugs had nearly three times the risk of depression and double the risk of anxiety and ­suicidal behaviour.

The findings echo earlier research published in JAMA Network Open in 2024, which analysed World Health Organisation safety data and found that people taking semaglutide were 45 per cent more likely to report thoughts of suicide or self-harm than those on other treatments.

One possible explanation is that GLP-1 receptors are found in the brain’s reward centre, where the drugs appear to dampen the effect of dopamine – the chemical that makes us feel pleasure and motivation.

Yet the evidence is mixed: Khalida Ismail, a professor of psychiatry and medicine at King’s College London, in a review of 80 trials involving 107,860 patients, in JAMA Psychiatry in 2025, found no evidence that GLP-1 drugs worsen mental health in clinical trials. As she told Good Health, ‘all nine of my patients in [another] study described improvement in wellbeing and psychological health. They all described a reduction in food noise. That anxiety and impulsiveness around food dissipated.’

And now the Food & Drug Administration in the US has just told Eli Lilly and Novo Nordisk (which make Zepbound – the US version of Mounjaro for weight-loss – and Wegovy and Saxenda respectively) to remove warnings about suicidal thoughts and behaviour from the labels. This followed a study involving 107,910 patients, which found no increased risk of suicidal ideation or behaviour, or other psychiatric side-­effects such as anxiety or depression. (The UK and EU have never had this warning in the first place.)

Yet there may remain concerns for people who are psychologically vulnerable. A study published in BMC Medicine last month found GLP-1 use was more common among people experiencing psychological distress. Professor Ismail says there is a worry about what happens when treatment stops if someone doesn’t have proper support. ‘When they stop it, everything comes flooding back,’ she says. ‘All the negative thoughts and feelings come back.’

For people with eating disorders – binge eating or emotional eating, for example – she warns that the drugs may suppress symptoms without addressing the underlying cause. Those patients, she explains, usually need psychological therapy alongside any medical treatment – but she says that is not happening enough.

Drugmakers stress that safety warnings are already in place.

Novo Nordisk told Good Health that gallstone disease occurred in 1.6 per cent of patients in Wegovy trials and is listed as a common side-effect. The company ‘believes that the allegations in the lawsuits are without merit, and we intend to vigorously defend against these claims’.

Eli Lilly says gallstones affect up to one in ten people using ­Mounjaro for weight loss, while pancreatitis is uncommon, affecting up to one in 100. It advises patients to discuss any history of pancreatitis or eye disease before starting treatment.

Despite the emerging concerns, doctors are clear that for the right patients, under proper medical supervision, these drugs can be life-changing. ‘These are overwhelmingly a source of good,’ says Professor Korner. ‘If someone has had a heart attack or stroke, you put them on this medication and you can reduce their risk of dying or having another event by around 20 per cent.’

But the benefits must always outweigh risks, adds Professor ­Pirmohamed: ‘That requires ­careful assessment of the ­individual patient and prescribing only when the balance is clearly in their favour.’