What do we really know about the long-term use of Mounjaro and Ozempic?

Independent

7 hours ago

The headlines a few weeks ago were as sensational as they were unsettling. ' Ozempic may stop the pill working properly,' this newspaper reported after the Medicines and Healthcare Products Regulatory Agency (MHRA) issued a warning: pill users should double up on contraception while using the jabs and avoid them altogether during pregnancy or breastfeeding. The British Menopause Society also added that women on HRT taking the drugs might fail to absorb progesterone pills, which could increase the risk of womb cancer.
Meanwhile, other reports warned that the injections many are using for weight loss, like Wegovy and Mounjaro, might also carry a hidden risk of kidney cancer.
And this month, the European Medicines Agency cautioned that semaglutide could double the risk of a rare sight-loss condition called non-arteritic anterior ischemic optic neuropathy (NAION).
These headlines would be alarming even if the drugs were rarely used. But these so-called weight-loss jabs have become so popular that even their manufacturers didn't anticipate the demand - and from this week, GPs are allowed to offer Mounjaro to obese individuals who also suffer from a range of other health complications.
As of March 2025, market intelligence company IQVIA estimated that around 1.5 million people in the UK were using weight-loss treatments. With limited NHS availability, roughly 80 per cent of these are purchased privately online and have made the pharma companies that make them some of the most valuable firms in Europe.
But with no real long-term studies, do we really know how safe these drugs are? While they will have been thoroughly tested before hitting the market, have manufacturers really considered how people are using them? What do we really know about their long-term effects? Is this truly a medical breakthrough – or just another chapter in the troubled history of slimming pills?
A crisis in need of solutions
There's no denying that obesity is a public health emergency. Nearly three-quarters of people aged 45 to 74 in the UK are now overweight, up from just over half in 1993. Obesity is linked to conditions such as type 2 diabetes, heart disease, joint problems, infertility, and around 30 types of cancer.
It's estimated to cost the NHS £6.5bn a year. Given this, the search for a safe, effective obesity drug has long been seen as medicine's holy grail. But past attempts have often ended in disaster, either due to limited results or serious safety issues.
The troubled history of slimming drugs
Weight-loss drugs have historically come with significant risks. One of the earliest, 2,4-dinitrophenol, was initially used as an explosive in the First World War. It worked by increasing metabolism, causing the body to burn calories as heat. As hemlines rose in the 1920s, flappers flocked to it, but it turned out that the wrong dose could literally cook users from the inside. Horrific deaths meant the drug was banned in 1938.
Later came amphetamine-based drugs, widely used in the Fifties and Sixties until their links to addiction and cardiovascular issues led to bans. More recently, sibutramine (Reductil) and rimonabant (Acomplia) were withdrawn after being linked to heart attacks, strokes, and psychiatric effects. By the time Acomplia was suspended in 2008, four trial participants had died by suicide.
Enter: GLP-1 agonists. These new-generation drugs, which include semaglutide and tirzepatide, were the first to mimic our own natural appetite-regulating hormones. The first to hit the market was exenatide – a drug to treat type 2 diabetes – in 2005. Ozempic was then approved in 2017 and Mounjaro in 2023. Clinical trials showed unprecedented weight loss of up to 26 per cent of body weight in some cases, on par with bariatric surgery – and seemingly without the deadly side effects of their predecessors.
So, why are these drugs different? 'Most previous drugs targeted the brain, which is where hunger lives,' explains Professor Giles Yeo, a molecular neuroendocrinologist at Cambridge University. 'But that led to serious side effects. These newer drugs are modified, longer-lasting versions of natural hormones – they're designed to go to the right brain regions naturally and for our body to respond to them in the same way they do to our own hormones.'
Miracle or minefield?
Despite their success, the rapid rise in use has triggered concern. Many users now access these jabs through private online clinics with minimal oversight. Some even acquire illegal 'compounded' medications from beauticians. Social media is flooded with user reviews, micro-dosing tips, and 'before-and-after' photos. But this week, a spokesperson for Novo Nordisk, which markets Ozempic and Wegovy, told the Daily Mail that practices like microdosing weren't recommended. 'The approved doses are the only dose strengths that have been studied and are licensed to use,' they warned.
Similarly, the Royal Pharmaceutical Society has warned that without proper supervision, users face risks including dehydration, gallstones, malnutrition, and muscle loss.
What do we know about long-term safety?
Yeo is optimistic: 'Regulatory bodies like the FDA and EMA are very rigorous. These drugs are approved globally, and they wouldn't be if they were deemed unsafe.'
Professor Carel le Roux, a metabolic medicine expert at Ulster University, adds that all approved drugs – not just weight-loss drugs – must be studied for at least 52 weeks. This is because, he says, 'If we haven't seen major issues by a year, we're unlikely to. And this is based on the regulators' experience of tens of thousands of previous studies.'
However, less obvious side effects often appear only after widespread use. Le Roux insists that the new findings that have dominated the headlines in the last few weeks are typical of standard 'post-market surveillance' by which pharma companies and regulators continue to collect data.
'Yes, things can emerge,' he says. 'But we've used this class of drugs for 20 years, mostly in people who were sicker than current users. The data is incredibly reassuring.'
Le Roux also points out that in trials, participants on these medications had fewer serious adverse events than those on placebo. 'That's because obesity and diabetes are so harmful themselves. There comes a point when it's unethical not to license a drug that can make people healthier.'
Untangling the risks
Some risks are still being studied. The kidney cancer alert came from a study of 43,000 people on GLP-1 drugs versus 43,000 controls. There were 83 cases in the treatment group compared to 58 in the control group – a slight absolute increase and not necessarily a clear causal link.
Conversely, other trials show strong kidney protection. The FLOW trial (2019–2023) followed over 3,500 patients and found a 24 per cent lower risk of kidney failure and a 50 per cent reduction in death from kidney disease among semaglutide users. The findings were so conclusive that the trial ended early in order to offer treatment to the placebo group.
Le Roux remains confident: 'We've shown these drugs can reduce heart attacks by up to 25 per cent and cut the risk of developing diabetes in people at risk by 80-90 per cent. Yes, eye issues have emerged, but this particular condition is only seen in people with diabetes, and the risk is around 1 in 10,000.' Yeo also points out that in fact, 'type 2 diabetes is the leading cause of blindness in adults'.
So, what about the contraceptive and HRT concerns? Le Roux says vomiting, a known side effect of the drugs, is likely to be to blame rather than the drug blocking absorption per se. 'Anything swallowed will eventually be absorbed – unless it's thrown up.'
To reduce nausea while on these drugs, he advises sticking with lower doses, even if that slows weight loss. If vomiting continues to be a problem, switching to non-oral forms of HRT, such as patches, or using condoms or a coil should eliminate the issue.
Osteoporosis and other risks
Others have expressed concerns about the effect of weight-loss injections on muscles and bones. US singer Avery, who took Ozempic for a year, despite having an eating disorder, recently tearfully revealed she had been diagnosed with osteoporosis. She admitted that she did not get the drug from a doctor. So how common is her experience?
A review published last year showed that between 15 and 40 per cent of weight loss with semaglutide could be lean tissue. Yeo says that it's something users should be aware of. 'Anyone losing weight by any means will always lose lean tissue – which includes water, muscle and bone – alongside fat.' However, he says there is no evidence this far that weight loss injections contribute independently to osteoporosis.'
Yeo says the best way to mitigate bone loss is with exercise, which studies show can preserve muscle and bone density when taken with these drugs.
A protein-rich diet also helps maintain muscle. Reviews have also shown that after weight loss, even though they lost lean tissue, people tended to end up with a higher proportion of lean mass compared to fat and that this muscle could be 'better quality' with stronger muscle fibres. However, in older people with fewer reserves, losing too much weight and muscle, which is harder to rebuild as we age, can be risky.
The problem of dependency
These drugs don't cure obesity – they manage it. Stop the injections and your appetite returns. One study found that patients regained two-thirds of the weight they had lost within a year of stopping treatment. This raises challenging questions. 'One of the most important questions we ask patients now is, 'Are you willing to take this medication for life?'' says Le Roux.
And of course, this comes at a cost, whether it's private consumption (roughly £250 a month) or the NHS, which will have to consider covering lifetime prescriptions. And with the huge sums involved, how do we protect against black-market misuse?
The next generation: hope or hype?
Current drugs target only one or two appetite-regulating gut hormones. However, as Yeo explains, around 20 gut hormones influence satiety. Next-generation treatments may combine more hormones, allowing lower doses and potentially fewer side effects, such as vomiting.
'These could reduce digestive side effects to zero,' says Yeo. Some new generation weight-loss medications are even being designed to protect muscle and bone mass by activating pathways that mimic the effects of exercise.
Yeo says that future, cheap pill forms of the drugs may also prove the secret to lifelong maintenance. With the World Health Organisation announcing in May that it plans to endorse anti-obesity drugs for adult treatment, access may expand globally which could be a medical turning point.
But they're not for everybody...
Few in medicine doubt that GLP-1 drugs mark a breakthrough. But they are not a one-size-fits-all solution. Around 15 per cent of patients don't respond. And there's growing concern that access remains limited to those who can afford private prescriptions, while NHS patients face restrictions. Many people take them without exercising or improving their diet, which is essential to preserve strong muscles and bones in the future.
However, Yeo believes that change is on the way. 'In seven years, Ozempic's patent expires. I predict the cost will fall from £200 to maybe £10 a month. When that happens, the NHS will be able to provide it widely – with proper supervision. These powerful drugs are designed to be used for health reasons, not as a cosmetic tool. They are designed to help people with obesity. If they are taken by skinny people, that's when side effects rocket and the risk vs benefit ratio changes. We need to keep them out of the wrong hands.'
Drugs like semaglutide offer a new weapon in the battle against obesity – a condition that has proven difficult to treat for decades and costs the NHS millions in comorbid conditions, which can range from type 2 diabetes, cancer, cardiovascular disease, osteoarthritis and even depression. But they aren't magic bullets. They come with risks, limitations, and hard decisions about long-term use.
Appropriately used, with medical oversight and realistic expectations, they can be life-changing. But the real test isn't just in the weight lost this year – it's what happens over the next decade.
We should welcome them, but with cautious optimism and our eyes wide open.