A weight-loss injection pen sits in Melanie Hinton’s fridge amid the eggs and vegetables she’s trying to train her brain to enjoy. She knows Saxenda, the brand she was prescribed, could help shift the fat that has crept on thanks to a double whammy of menopause and biscuit addiction.
And, at 12st 10lb and 5ft, she’s desperate for a solution where slimming clubs and willpower have failed.
‘My confidence has gone. I feel depressed. I have osteoarthritis and degenerative disc disease and the excess weight is limiting my mobility,’ says Melanie, 56, a married mother of two from Leicester.
But a month ago, when she injected herself with the medication, which contains the drug liraglutide and like the better-known semaglutide mimics the action of the GLP-1 hormone to reduce appetite, she felt so sick she couldn’t get out of bed for 24 hours. While nausea is a side-effect that supposedly passes, she’s too scared to try again.
‘Putting a needle in myself makes me feel weak,’ she says. ‘If I could get the same results from a pill, it would make a massive difference. In tablet form, I’d get it down.’
She won’t have to wait long. At least a dozen oral versions of the weight-loss jabs that have revolutionised our attitude to dieting in just two years are being created, with a couple already on the cusp of completion.
With research suggesting they can cut cravings in a similar way to injectables such as Wegovy and Mounjaro, these pills look set to upend the weight-loss landscape all over again – and perhaps to an even greater extent.
After all, what could be more convenient than popping a pill, with no fridges, forward thinking or punctured skin required? In tablet form, GLP-1 drugs will not only be more appealing to people like Melanie, but potentially cheaper and certainly easier to roll out on a mass scale to the billions who are overweight or obese worldwide.
When Melanie Hinton injected herself with Saxenda, she felt so ill she couldn’t get out of bed for 24 hours. If it came in a pill form, Melanie would be able to take the weight-loss drug
Indeed, this week Sir Tony Blair’s think-tank suggested the NHS send injectables through the post, to speed up delivery and get those whose health is affected by obesity off benefits and back to work. Imagine how much easier that would be with a blister pack of pills compared to bulky, temperature-sensitive jabs.
Already the markets are poised. Whether weight-loss pills expand an industry already estimated to reach £75 billion in sales by 2030, or, as some experts believe, come to dominate it, they will certainly offer a windfall to the pharmaceutical giants creating them.
Little wonder, then, there is a race to get them to the public first, with every step closer sending the stakes higher.
Last month, when Eli Lilly became the first company to successfully complete a phase 3 trial for a small-molecule weight-loss pill (more of which later), its share price rocketed by 13 per cent.
‘The company that has the best effects is at such an advantage that everyone is trying to take a share of the market,’ says Professor Elisabet Jerlhag Holm, an addiction researcher at the University of Gothenberg, who studies the efficacy of these drugs.
So who are the behemoths battling it out? Which will get there first? And how will our lives change as a result?
On paper, Novo Nordisk, the Danish company that started the weight-loss jab movement with Ozempic, the injection licensed for diabetes in the UK back in 2019, is winning. Last month it was the first to submit a GLP-1 weight-loss pill for approval to America’s Food and Drug Administration (FDA), which is expected to make a decision on the drug’s viability by the end of the year, meaning it could be on the market as early as 2026.
In phase 3 trials – the final stage in the clinical trial process – the pill, an oral version of Wegovy (the weight-loss version of Ozempic, licensed in the UK in 2023) led to an average weight loss of 15 per cent over 68 weeks – a similar amount to injectable Wegovy.
‘The company that has the best effects is at such an advantage that everyone is trying to take a share of the market,’ says Professor Elisabet Jerlhag Holm
Novo Nordisk arguably had the edge because it has already developed the first GLP-1 pill shown to cause weight loss – Rybelsus, licensed for diabetes since 2019.
Sarah Coombs, 77, a diabetic, has been taking it for eight months. She is one of 20,000 participants on a five-year trial run by Oxford University, testing the effects of Rybelsus on heart health, after being put forward by her GP. Within a week of taking the ‘small, oval, bitter’ pill last September, her appetite drastically diminished.
‘That constant hum in the background — what will I eat next? — was gone. If I eat too much fat, I feel queasy. I’ve cut my portions down. I just can’t eat as much,’ says the grandmother from East Stour, Dorset, who had tried various ways to lose weight, from juicing retreats to egg-based diets, with little success. ‘The simplicity of the pill has made me feel safe,’ says Sarah, who has shrunk from 11st 5lb to 10st 5lb.
So far, so promising. However, both Rybelsus and oral Wegovy’s active ingredient, semaglutide, is a peptide (a short chain of amino acids) too big to be efficiently absorbed from the gut into the bloodstream – so a pill needs to contain a greater amount than its injectable version which of course bypasses the gut altogether. Sarah is taking a 14mg dose, while oral Wegovy contains a whopping 25mg, compared to just 2.4mg in highest dose of the Wegovy jab.
What’s known as a ‘gastrointestinal permeation enhancer’ also has to be added to the pills to ease penetration, explains Prof Jerlhag Holm. The one in Rybelsus, for example, is called salcaprozate. Even then, ‘gastrointestinal absorption can break down medications, resulting in disappointing results’, adds Lee Brown, a health care analyst at investor research firm Third Bridge.
It can also mean more significant gastrointestinal side-effects, according to Dr Jorge Moreno, an obesity specialist and assistant professor of medicine at the Yale School of Medicine.
Certainly, Sarah’s nausea has worsened since her dose was increased from 7mg to 14mg: ‘I have some days where I feel rotten.’ She has experienced hair loss – a reported side-effect of semaglutide. ‘It could be my age, but I don’t want it to get doubly thin because I’m taking a funny pill. I also get more heartburn now.’
Plus, she has to take her Rybelsus tablet on an empty stomach, then wait 30 minutes before eating – and the same will go for oral Wegovy – which rather takes the edge off the convenience factor.
Sarah Coombs has been taking Rybelsus for eight months on a five-year trial from Oxford University
The active ingredients in other weight-loss injections, such as liraglutide in Novo Nordisk’s Saxenda and tirzepatide in American company Eli Lilly’s Mounjaro, are also peptides, and so also likely to be problematic in pill form.
Which explains why ‘small molecule’ weight-loss pills that have the same impact on GLP-1 receptors as injectables and can be absorbed through the gut are the holy grail of tablet solutions.
Effectively this is a brand new formulation of a GLP-1 drug.
Eli Lilly’s is called orforglipron – and it’s also the reason why, even though it hasn’t yet been submitted for approval, the company still has the edge over its competitors.
Although results were only reported last month for its trial on people with diabetes – it is expected to report on its trial on obese participants ‘later this year’ – participants lost an average of 16lb in 40 weeks taking the once-daily pill.
Orforglipron ‘can be taken any time of the day without restrictions on food and water intake’, says Patrik Jonsson, executive vice president and president at Lilly Cardiometabolic Health.
The company expects to submit orforglipron for approval by the end of this year. In the UK drugs are given the green light by The Medicines and Healthcare products Regulatory Agency, which takes an average of six months to approve a drug, unless it has already been approved by other authorities such as the FDA or European Medicines Agency in which case it can be fast tracked in as little as two months – meaning as soon as next summer, popping an orforglipron pill could be as much a part of our daily routine as brushing our teeth or walking the dog.
Eli Lilly’s CEO David Ricks could be forgiven for feeling smug as he told Time magazine last month that if orforglipron – developed by the Japanese pharmaceutical company Chugai and effectively bought for commercial purposes by Lilly in 2018 – proves successful, ‘it will go down as probably the best business development deal in the history of pharma’.
David Ricks is the CEO of Eli Lilly, which last month became the first company to successfully complete a phase 3 trial for a small-molecule weight-loss pill
Yet the race is not won yet. The approval process for any new drug is notoriously difficult, and a medication that has taken years and cost a fortune to get to this stage (Lilly’s average cost to discover and develop a new drug is £1.9 billion) can still be failed by authorities for something as innocuous as its manufacturing process.
Or an unexpected side-effect could floor it at the final hurdle. Last month Pfizer announced it was discontinuing development of its small molecule weight-loss drug danuglipron after one ‘asymptomatic’ subject in a 1,400-participant strong phase 3 trial experienced ‘potential drug-induced liver injury’.
If a company has similar promising drugs in its pipeline, it can bounce back better from a trial failure, but when data doesn’t live up to the hype, heads roll. Last week, after disappointing results, Novo Nordisk’s CEO Lars Fruergaard Jorgensen, left the company, a departure euphemistically described as the result of ‘market challenges’.
The ubiquity of Ozempic and Wegovy long made Novo the market leader, but they target one receptor that influences appetite (GLP-1), unlike Lilly’s newer Mounjaro, which targets two (GLP-1 and GIP) and which now seems more popular. According to a trial (admittedly funded by Lilly) presented to European Congress on Obesity this month, Mounjaro led to 20 per cent weight reduction after 72 weeks of treatment, pipping Wegovy’s 14 per cent. ‘Confidence is greater with Eli Lilly,’ says Sheena Berry, healthcare analyst at Quilter Cheviot, who attributes Jorgensen’s departure to Novo’s share price performance as well as the ‘market challenges’.
In a cut-throat industry, one company’s triumph is another’s despair. ‘If a rival company releases better results (say, greater weight loss or fewer side-effects) then other companies’ stocks can fall, even if their own trials were OK,’ says Pernia Rogers, financial analyst and founder of finance company Your Finance Travel Buddy. Last June, for example, Eli Lilly announced that its latest injectable weight-loss drug, retatrutide, achieved a 24 per cent weight loss in trials. In December 2024 Novo Nordisk revealed that its new injectable weight-loss drug, CagriSema, achieved a very slightly lower weight loss, at 22.7 per cent. ‘The poor comparative performance saw a drop in stock price of 20 per cent – a wipeout of £76 billion in (Nova’s) market value,’ says Rogers.
Unsurprisingly, pharma companies are cagey about discussing their drugs before trials are completed. But Astra Zeneca, whose small molecule GLP-1 drug, AZD5004, is in phase 2 trials, did allow me to speak to its senior vice president Mikhail Kosiborod, a lead scientist in its development.
Last year early trial data found 5.8 per cent weight loss in participants with diabetes after four weeks on the drug, but Kosiborod is ‘certainly not’ prepared to speculate on how his drug compares to his rivals at this stage in the research. ‘We’ll have to wait and see once we have the data.’
There is, he believes ‘a remarkable simplicity and convenience of having a once-daily pill’, adding that ‘a pill that doesn’t need to be refrigerated and can be easily distributed to hundreds of countries is incredibly powerful’.
Astra Zeneca senior vice-president Mikhail Kosiborod believes there is a ‘a remarkable simplicity and convenience of having a once-daily pill’
Plus, a small molecule medication can be combined with other medicines for serious conditions like heart failure. ‘Our approach is to focus not just on weight loss but to provide maximum value to the patients by reducing complications, and we believe by combining AZD5004 with other treatments in our portfolio we can deliver that.’
Astra Zeneca, whose HQ is in Cambridge, has a ‘long legacy’ in developing small molecule drugs and is a ‘truly global company’ he says. ‘Our ability to mass produce treatments to address the needs of potentially hundreds of millions of patients is super important. That’s what we bring to the table.’
Smaller companies such as Structure Therapeutics and Terns Pharmaceuticals – based in the US – are also developing GLP-1 pills, while manufacturer Syntis Bio, another American company, is trialling a weight-loss pill called SYNT-101 that stops food from being absorbed.
Many doctors think pills will serve as a way of maintaining or boosting weight loss once initial weight has been lost through injections, says Lee Brown: ‘Alternatively, they see the market breaking down with higher BMI patients using injections and lower BMI patients using orals.’
Certainly, they are a less drastic prospect for those without a huge amount to lose, like Sarah Coombs. She’s not overweight enough to qualify for an Ozempic prescription from her doctor, yet felt ‘disappointed and a bit ashamed’ as her weight crept on.
Whether pills will become as integral a part of a dieter’s tool kit as cottage cheese and chicken breasts remains to be seen, but after years of fighting her weight and health, Sarah is delighted to have shed pounds on the oral semaglutide trial. ‘My waistbands feel looser – and I may fit into my favourite summer dress again.’
Additional reporting by Rosie Beveridge