The first two GLP-1 weight loss drugs that can be taken daily in pill form rather than via weekly injections are predicted to be licensed before the end of the year.
Here’s what you need to know:
The blockbuster weight loss jabs Wegovy and Mounjaro have taken the UK by storm, with 1.6 million packs sold every month, and people paying up to £250 a month for them privately according to sales figures from the National Pharmacy Association.
The NHS is also providing the jabs to 200,000 people who meet strict criteria through weight management clinics over three years.
The active ingredient of the weight loss jabs marketed under brand names Wegovy and Ozempic is semaglutide. It works by acting on GLP-1 receptors in the body, suppressing hunger hormones and slowing gastric emptying, so that you feel fuller for longer.
Tirzepatide, the active ingredient of Mounjaro, also targets GLP receptors and another hormone receptor called GIP (glucose-dependent insulinotropic polypeptide).
“Both are weekly injections, but many people would prefer the convenience of a pill,” says Giles Yeo, professor of molecular endocrinology at the University of Cambridge and programme leader at the MRC Metabolic Diseases Unit.
“Now, two new GLP-1s – both daily pills – have completed phase three clinical trials (where a drug is compared with a placebo or an existing treatment) and are expected to be approved in the next few months.”
The pill most likely to be approved first is a 25mg semaglutide tablet made by Novo Nordisk, the Danish pharma company behind Wegovy/Ozempic.
An application was made to the US Food and Drug Administration (FDA) earlier this year, and it's anticipated that approval will be granted by the end of 2025, with a commercial launch in early 2026 likely.
Trials have shown that semaglutide injections helped obese and overweight people lose 15 per cent of their body weight over 64 weeks, when combined with a reduced calorie intake and increased physical activity.
More recent research has shown that patients taking oral semaglutide achieved weight loss of between 12 and 15%.
Prof Yeo says: “The manufacturer has taken an interesting approach by concentrating the active ingredient semaglutide into quite a high dose in the daily pill in order for it to survive the stomach.
“This means that, although the cost of needles is avoided, the price won’t be significantly cheaper because they are having to put so much more of the drug – 10 to 100 times – into it.”
Not necessarily, says Prof Yeo. “It is slightly less effective than the injectable form,” he explains, “and we'll have to see if the higher dose increases side effects – particularly the gastric ones.”
Eli Lilly, the US company that launched Mounjaro (currently regarded as the “King Kong”of weight loss drugs) is also planning to submit an application for its new pill, Orforglipron, for licensing at the end of the year.
Trials have shown that overweight or obese people on the highest daily dose of 36mg can lose an average of 12% of their body weight over 16 months. Researchers also found that it improved systolic (top number) blood pressure, cholesterol levels and blood fats (triglycerides).
This, however, is less than injectable Mounjaro provides – when combined with a 12-week exercise and diet lead-in, users of the injectable version achieved an average weight loss of 26.6% over 84 weeks.
“This is a ‘white powder’, small molecule drug, which means it’s stable on the shelf and therefore dirt cheap to make,” says Prof Yeo.
“It won’t be that much less expensive to start with, but once it comes off patent, it will be as cheap as drugs such as Panadol [paracetamol] or a very cheap statin, and it will be far easier to get out to low-resource countries.”
Prof Yeo says that around 3.43 million people in the UK are currently eligible for weight loss jabs, according to strict criteria set by the National Institute for Health and Care Excellence (NICE), but only 200,000 will get them on the NHS over the next three years.
“At the moment, the people who are not getting the drugs are the ones who need it the most. When the drugs become cheaper, more people will have access to them.”
“Practically every major pharmaceutical company and some smaller biotech companies have a GLP-1 drug in development,” says Prof Yeo.
“There are well over a hundred. Some will fall flat on their face, but others will make it to market. Generally, the drugs that are being developed are going to be even more effective and have fewer side effects.”
He adds: “All the drugs have a GLP-1 backbone – that’s the known quantity in weight loss drugs. It stops hunger and makes you feel full. Then there's a smorgasbord of whatever else they're targeting.”
Prof Yeo says that some of the drugs aim for “high-quality” weight loss, meaning they will preserve muscle mass as well as aid weight loss. Sarcopenia (loss of muscle mass) can be a concern with rapid weight loss and in older people generally. “Some companies are trying to mix compounds that target sarcopenia with their GLP-1s,” Prof Yeo points out.
Other promising drugs in the development pipeline include Amgen’s MariTide, which is beginning a phase three trial. MariTide’s phase two trial reported weight loss of up to 20% at 52 weeks, with no weight loss plateau.
“This is a once-monthly injection, so it will still have the challenge of the cold chain [the injection has to be kept in the fridge until first use], but some people would rather have a monthly injection rather than a daily pill,” says Prof Yeo.
MariTide’s phase three trials are scheduled to report in 2027, so if the drug is approved it’s not expected to be available until at least 2029.
Pfizer terminated the development of its weight loss pill danuglipron in April this year after a patient developed liver injury during a trial.
So far, doctors have discovered that GLP-1s can also lower blood pressure and cholesterol, and improve kidney disease, type-2 diabetes and non-alcoholic fatty liver disease, says Prof Yeo.
“The big question now is whether semaglutide [the active ingredient of Ozempic and Wegovy] can slow down and protect against Alzheimer’s.
“A big trial that is testing this hypothesis is due to report this month [October]. If semaglutide is found to work, then it’s another big game changer as there are currently very few disease-modifying Alzheimer’s drugs available.
“And semaglutide would be much cheaper than the monoclonal antibodies or MABs [such as lecanemab and donanemab] that NICE currently won’t approve because of their high cost. This would be a treatment that would be more affordable for the NHS.”
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