As Wegovy jab becomes available on the NHS… Here’s how the next weight-loss drug could be a PILL (and it may be cheaper with fewer side-effects)
New, more effective weight-loss drugs may soon overtake the current blockbuster slimming injections Ozempic and Wegovy.
The good news is these new drugs not only have fewer gastric side-effects, but some of them also come as pills, rather than having to be injected.
Wegovy (generic name semaglutide) can help obese people lose up to 15 per cent of their weight, and when it was launched in the U.S. for weight loss in 2021 it was seen as a breakthrough in tackling the growing global obesity and type 2 diabetes epidemics.
Just last month, new data from a five-year trial of Wegovy suggested it could cut the risk of a heart attack or stroke in obese people with cardiovascular disease by a fifth.
Ozempic, another weekly injectable that contains the same active ingredient, semaglutide, is currently only available on the NHS as a treatment for type 2 diabetes, and not specifically weight loss.
New, more effective weight-loss drugs may soon overtake the current blockbuster slimming injections Ozempic and Wegovy
But such is its effectiveness that some doctors do prescribe it for obesity, with a private prescription costing around £300 a month.
In March, the National Institute for Health and Care Excellence (NICE) approved the use of Wegovy with diet and exercise as part of NHS specialist weight-management services.
It’s available to people with a BMI of 35 and above who also have a weight-related condition such as high blood pressure, pre or type 2 diabetes or sleep apnoea.
Those with a BMI of 30 to 34 are eligible, too, if they also have a weight-related health condition and meet the criteria for referral to a specialist weight-management service.
But both these ground-breaking drugs have to be self-administered weekly, using an injection pen, and side-effects include nausea, diarrhoea and constipation.
There are reportedly two dozen second-generation weight-loss drugs in development that aim to improve on the benefits, and have fewer side-effects.
One is retatrutide, a weekly injection which, during clinical trials, led to an average 24 per cent weight loss (or 58lb in weight) in 48 weeks, according to results published in the New England Journal of Medicine in June.
This is the biggest weight reduction achieved by any drug so far. Those on retatrutide all lost at least 5 per cent of their body weight and, crucially, at the end of 48 weeks, they were still losing weight, with no sign of a plateau.
Retatrutide also contains semaglutide, that works by mimicking a hormone called glucagon-like peptide 1 (GLP-1), which is released in response to food and reduces the appetite, and slows stomach emptying, so you feel full for longer.
But retatrutide targets two other hormone receptors as well as those for GLP-1: these are GIP and glucagon. All three have the net effect of reducing appetite.
Obesity expert Giles Yeo, a professor of molecular neuro-endocrinology at the University of Cambridge, told Good Health that the retatrutide results were ‘absolutely remarkable’.
‘The results caused quite a stir at the American Diabetes Association meeting in San Diego in June, as the weight loss achieved is approaching the 30 per cent figure we get in patients who’ve had bariatric surgery [such as a gastric bypass].’
The retatrutide trial was a phase 2 trial – i.e. a small study that looked at safety and efficacy.
‘If these findings hold up in phase 3 studies [where the drug is trialled in a larger group and compared with a placebo], retatrutide could be an option for people who are very obese who don’t want surgery and would prefer an injection,’ says Professor Yeo.
‘These drugs all have the same mechanism of mimicking hormones that control appetite, but retatrutide goes after three hormone receptors instead of one.
‘We don’t know the exact mechanism yet, but we think this combined approach may be more effective as the brain is getting these messages in bulk.’
This triple-whammy, says Professor Yeo, convinces the brain that the gut is full when it isn’t, ‘so people eat less’.
And because it targets three hormone receptors, he says, it may mean the amount of each active ingredient could be reduced, potentially lowering side-effects compared with existing GLP-1 mimickers. Although retatrutide has similar gastric side-effects to semaglutide – mainly constipation, diarrhoea and nausea – the recent trial showed they were less severe.
Orforglipron is another new drug which works in a similar way – but its big advantage is that it comes as a tablet.
In trials, it led to average weight loss of 14.7 per cent of body weight in nine months, according to results in the New England Journal of Medicine in July. This is comparable to Wegovy.
Scientists developed weight-loss drugs initially as injections to avoid the ingredients being destroyed by stomach acid, says Professor Yeo.
‘Lots of people may prefer taking a daily pill to an injection, especially if they are needle-phobic; others may prefer a once-a-week treatment. Pills will be cheaper to produce, too.’
(Injections can cost around £300 a month privately.) A rival daily pill, called Rybelsus, is an oral version of Ozempic, with the same active ingredient, semaglutide and is approved for treating type 2 diabetes in the UK.
Although it’s not a weight-loss drug, people do lose weight taking it; one study found up to 8lb in six months, depending on the dose.
Meanwhile, HU6 – a pill being developed by U.S. firm Rivus Pharmaceuticals – appears to yield similar results to GLP-1 drugs, but works in a different way.
It’s the first in a new class of weight-loss drugs called controlled metabolic accelerators, which harness a natural process in mitochondria, the ‘battery’ in our cells, to increase the breakdown of fat and sugar and increase resting energy expenditure.
The next generation of medicines could be on the market within a couple of years, says Professor Yeo.
‘All these drugs are giving overweight and obese people more options, and obesity is becoming a treatable illness,’ he adds.
‘If you take Ozempic, for instance, all you’re doing is changing one hormone in your body a little bit. What this tells us is that obesity is not some internal moral failing; it’s a hormonal problem.’
However, Professor Yeo stresses that weight-loss drugs will work only while you’re taking them, and that you’ll regain your appetite when you stop.
And he says more long-term safety data is needed: ‘NICE has approved Wegovy for two years’ use for each patient, as we have only two years’ safety data.’
‘Skinny’ jab started my weight loss, but the Fast 800 kept it off
Dr Pawel Gadomski, 45, an A&E consultant in Greater Manchester, reveals how a dual approach has been key to his staying slim. He says:
As a doctor, I’m acutely aware that medical science doesn’t always have all the answers. But when I had a serious weight problem, there was no big mystery about its cause: I ate too much and I didn’t exercise.
I’d always been a bit chubby, but I really started to gain weight after moving to the UK in 2006 to work as a doctor. By 2020, I’d ballooned to 24st. At 5ft 11in, this put my BMI at 47 (over 30 is obese).
I did actually dabble with diets, but found it hard to count calories and lacked willpower.
Dr Pawel Gadomski, 45, (pictured left and right), reveals how a dual approach has been key to his staying slim
Catching Covid in March 2020 was the turning point. As a man in his 40s with high blood pressure, I was at greater risk of serious complications. I knew something had to change – and I knew I needed something dramatic to get me started.
As access to healthcare was limited due to the pandemic, I researched the options myself before deciding on the daily, self-administered weight-loss jab, Saxenda [similar to Wegovy, see main story], from an online pharmacy. Saxenda copies the action of a hormone – glucagon-like peptide (GLP-1) – that regulates appetite. But I also recognised I needed a plan for sustainable healthy living long-term, not least given the cost of the drug (around £300 a month).
In January 2021, I watched a TV interview with Dr Michael Mosley about The Fast 800. This is where you eat no more than 800 calories a day, before switching to two days a week of a moderately low-carb, Mediterranean-style diet, rich in protein, fibre and healthy fats, and following a tailored exercise plan. I realised this was what I needed in conjunction with Saxenda.
I began the injections in February 2021 and they took effect pretty rapidly, suppressing my hunger. I also followed the new diet regimen: cooked everything from scratch, strictly controlled portion sizes and used kitchen scales for the first time, and did 30 minutes’ exercise a day. The results were dramatic: I lost one-and-a-half stone in a month! Within a couple of months, my shirt size went from XXXL to L.
After five months, I weaned myself off Saxenda, continuing with the Fast 800. Today, 10st lighter, I feel so much fitter.
So why hasn’t my willpower failed this time? Well, I’ve been buoyed by knowing I’ve lost weight through healthy living. Most importantly, I no longer need food to feel better. I just regard it as fuel.
Injectable weight-loss drugs are a game changer, but they are not a panacea.
Once I quit Saxenda, the weight would have piled back on if I hadn’t addressed my unhealthy lifestyle. There’s no point in having the injections without some kind of structured approach to healthy living. No drug in the world can sort that bit out.
INTERVIEW: ANGELA EPSTEIN