A little over two years ago, a whisper of a new drug was abundant. Ozempic was quickly deemed a “miracle” medication, though few could predict how quickly and vastly it would revolutionise the weight loss industry. It swiftly became a coveted accessory in Hollywood, a status symbol of sorts and, for many, a go-to injectable tool for dramatic “before and after” transformations.
Since then, the “Ozempic era” has evolved through cycles of skepticism, celebrity denials (quickly followed by admissions, Oprah included), a supposed “baby boom”, serious side-effect concerns (nausea, headaches, vomiting, diarrhea), and the notorious “boomerang” weight gain once treatment ends.
Yet demand remains insatiable. GLP-1 receptor agonists like Wevogy and Mounjaro are more popular than ever and gain, even triggering global shortages that are leaving those with type 2 diabetes, who the drug was initially prescribed for, scrambling for access.
As a result, prescriber crackdowns targeting BMI falsificatons have begun and prices continue to rise, now approaching around £300 per month in the UK. And developments are constantly underway. In July 2024 the Medicines and Healthcare products Regulatory Agency (MHRA ) approved semaglutide for reducing cardiovascular risk in overweight or obese adults with established heart disease – a significant step beyond its role in weight management – and, crucially, now it seems an oral pill revolution is advancing.
According to reports, Britain could soon find itself at the centre of the next frontier in weight-loss drugs: the pill. Orforglipron, Eli Lilly’s new once-per-day tablet, is being billed as nothing short of a “game-changer.” If approved, it could arrive as early as next year.
The promise is seductive. Last month clinical trials showed that the drug helped patients shed an average of 12.4 per cent of their body weight which, although less than the most powerful injections, is a significant achievement. What’s more, it could be worth upwards of $100 billion by 2030. In everyday terms, it could mean that millions who currently inject themselves with Ozempic or Mounjaro every week might simply reach for a tablet with breakfast.
Patrik Jonsson, Eli Lily’s European president, has spoken openly about chasing the holy grail: a “once-and-done” treatment for obesity. “If we could be the ones that bring a once-and-done to treating obesity, that would be a huge contribution to humanity,” he said recently, while admitting that such a breakthrough is still many years away.
Like injectables, orforglipron works by targeting GLP-1 receptors, which suppress appetite and slow digestion, essentially keeping users fuller for longer. But unlike the jabs, the pill doesn’t require refrigeration and can be taken at any time of day, with or without food. It’s also expected to be cheaper to manufacture and distribute, a point that could prove crucial as systems grapple with demand that has already outweighed supply.
As those developments continue to bubble away in the background, a new market is rapidly expanding. Late last year saw an onslaught of “natural” alternatives from countless wellness brands that claim supplements or patches can increase the hunger-regulating hormone that GLP-1 agonists target without the need for injectables.
Kind Patches’ “GLP-1 Patches”, which cost £12 for a 30-day supply, supposedly “help you feel full longer, stabilize blood sugar levels and curb cravings”, are sold out; in September Kourtney Kardashian Barker’s wellness brand Lemme launched a similar product. A year before that, Halle Berry took on a role as chief communications officer (as well as being an equity owner) at biotech company Pendulum Therapeutics, which sells a GLP-1 boosting probiotic.
But another startup is doing things slightly differently. US-based Metabolize claims its metabolite-driven product could “redefine the weight loss landscape”. The supplement is taken orally and, essentially, mimics the proven benefits of the keto diet. Based on animal studies already conducted, the company believe their product can provide a 10-20 per cent weight loss with regular use.
“A couple of years ago there was an article published in Nature about an exercise pill that was based on a molecule called lactate phenylalanine,” Dr Morris Laster, a physician by trade who founded the company, tells me over Zoom. The paper was written by Dr Jonathan Long, an associate professor of pathology at Stanford University, and showed that when the molecule is targeted and increased, it suppresses appetite, decreases obesity and improves glucose regulation.
“I called him up,” Laster continues, “and he said, ‘Look, this molecule is great. But there’s one big problem with it – you can’t take it by mouth, you have to inject it.’ Six months later he showed me the results of what we now call ketone phenylalanine. What he found was that ketone phenylalanine and lactate phenylalanine are created by the same enzyme, BHB-phenylalanine – these are all increased by strenuous exercise, intermittent fasting and a ketogenic diet.
Their mechanism of action is very similar, so we hit the same receptors in the brain that are involved in long-term appetite suppression. We know that there’s a direct correlation between lactate phenylalanine in the blood and weight loss. And the benefit of ketone phenylalanine is that it’s orally available.”
Essentially, they claim that their product regulates appetite through distinct brain-based neural pathways – and their method is a first-of-its-kind metabolite-driven therapeutic which is safe, cheap and, crucially, side-effect free.
“Ozempic, GLP-1s, all of them do an amazing job for weight loss, but they have a number of side effects beyond the sheer cost of it,” Laster explains. “More than 80 per cent of people who are on them stop taking it within a year, 30 per cent within the first month. There are issues of panic with its potential for thyroid cancer, you feel nauseous often, you can have vomiting and diarrhoea.
“In addition to that, I think one of the big issues is that people don’t realise that the GLP-1 molecule itself, it’s in the pleasure centre of the brain. To use a colloquialism, it inhibits that dopamine squirt you get in the brain, which is essential for pleasure. And, unless you really modify your diet and lifestyle, once you stop taking the drug you will regain the weight.”
Metabolize, he claims, can act as an alternative to “bio-hack” your metabolic system, or as a “ramp” for people worrying about coming off GLP-1 agonists. The effects won’t be so immediate, or drastic – but it could provide a softer, effective way to manage weight long term.
The company is now in the process of getting Metabolize approved as a food ingredient – but hopes to license the product out to food companies to include in “protein bars, snacks” and as a food supplement by next year.
Perhaps it sounds too good to be true – only time will tell. But you can see why the race to find Ozempic alternatives or accompaniments like Metabolize is on: just recently, a new report said that an estimated 3.4 million Brits meet the criteria to receive a prescription for Wegovy and Mounjaro, which would cost £10bn a year. It could potentially bankrupt the NHS.
This is a market that is rapidly evolving. Novo Nordisk is anticipating that the next developments across the industry are likely to “narrow the gap” between weight loss fuelled by medicine, rather than risky surgical procedures. Elsewhere there’s potential in obesity treatment that targets entero-pancreatic hormones that are released while we actually eat. The science is bamboozling, but the effects could be monumental for healthcare. It looks as though the weight loss revolution is only just beginning.