Now that Wegovy jab becomes available on the NHS…Here’s how the next weight loss drug could be a PIL (and it could be cheaper with fewer side effects)

New, more effective weight loss drugs may soon overtake the current blockbuster weight loss injections Ozempic and Wegovy.

The good news is that not only do these new drugs have fewer side effects on the stomach, but some of them are also available in pill form, rather than having to be injected.

Wegovy (generic name semaglutide) can help obese people lose up to 15 percent of their weight, and when it launched in the US in 2021 for weight loss, it was seen as a breakthrough in tackling the growing global epidemics of obesity and type 2 diabetes . .

Last month, new data from a five-year trial of Wegovy suggested it could reduce the risk of heart attack or stroke in obese people with cardiovascular disease by a fifth.

Ozempic, another weekly injection containing the same active ingredient, semaglutide, is currently only available on the NHS as a treatment for type 2 diabetes, and not specifically for weight loss.

But its effectiveness is so great that some doctors 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 along with diet and exercise as part of the NHS’s specialist weight management services.

It is 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 apnea.

Those with a BMI of 30 to 34 are also eligible, if they also have a weight-related health condition and meet the criteria for referral to a specialist weight management service.

But both of these groundbreaking drugs must be self-administered weekly using an injection pen, and side effects include nausea, diarrhea and constipation.

There are reportedly two dozen second-generation weight-loss drugs in development that aim to improve benefits and have fewer side effects.

One of these is retatrutide, a weekly injection that led to an average weight loss of 24 percent (or 58 pounds in weight) over 48 weeks in clinical trials, according to results published in June in the New England Journal of Medicine.

This is the largest weight reduction achieved by any drug to date. Those who received retatrutide all lost at least 5 percent of their body weight and, crucially, at the end of the 48 weeks they were still losing weight, with no signs of plateauing.

Retatrutide also contains semaglutide, which works by mimicking a hormone called glucagon-like peptide 1 (GLP-1), which is released in response to food and reduces appetite and slows stomach emptying so you feel fuller for longer.

But retatrutide also targets two other hormone receptors in addition to 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 neuroendocrinology at the University of Cambridge, told Good Health 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 approaches the 30 percent we get in patients who have undergone bariatric surgery (such as gastric bypass).”

The retatrutide trial was a phase 2 trial, ie a small trial looking at safety and efficacy.

“If these findings hold up in phase 3 trials (where the drug is tested in a larger group and compared to a placebo), retatrutide could be an option for people who are very obese and don’t want surgery and 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 because the brain receives these messages in bulk.”

This triple whammy, Professor Yeo says, 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, this could mean reducing the amount of each active ingredient, potentially reducing side effects compared to existing GLP-1 mimics. Although retatrutide has similar stomach side effects to semaglutide – mainly constipation, diarrhea and nausea – recent research showed these to be less severe.

Orforglipron is another new drug that works in a similar way, but the big advantage is that it comes in tablet form.

In studies, it led to an average weight loss of 14.7 percent of body weight in nine months, according to results in the New England Journal of Medicine in July. This is similar to Wegovy.

Scientists initially developed weight-loss drugs as injections to prevent the ingredients from being destroyed by stomach acid, says Professor Yeo.

“Many people may prefer to take a pill daily rather than an injection, especially if they are needle phobic; others may prefer a once-a-week treatment. Pills will also be cheaper to produce.’

A rival daily pill called Rybelsus is an oral version of Ozempic, containing the same active ingredient, semaglutide, and is approved for the treatment of type 2 diabetes in the UK.

Although it is not a weight loss drug, people do lose weight when they use it; one study found up to 8 pounds in six months, depending on dose.

Meanwhile, HU6 – a pill being developed by US company Rivus Pharmaceuticals – seems to produce 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 use a natural process in the mitochondria, the “battery” in our cells, to increase the breakdown of fat and sugar and reduce resting energy expenditure. increase.

The next generation of drugs could be on the market within a few years, says Professor Yeo.

“All of these drugs are giving overweight and obese people more options, and obesity is becoming a treatable disease,” he adds.

“For example, when you take Ozempic, you’re just changing a hormone in your body a little bit. What this tells us is that obesity is not an internal moral failure; it’s a hormonal problem.’

However, Professor Yeo emphasizes that weight-loss drugs only work if you take them, and that you regain an appetite when you stop taking them.

And he says more long-term safety data is needed: “NICE has approved Wegovy for two years of use for each patient because we only have two years of safety data.”

The ‘skinny’ jab started my weight loss, but the Fast 800 stopped it

Dr. Pawel Gadomski, 45, an emergency room consultant in Greater Manchester, reveals how a dual approach has been key to staying slim. He says:

As a physician, I am well aware that medical science does not always have all the answers. But when I had a serious weight problem, there was no great mystery about what caused it: I ate too much and didn’t exercise.

I’ve always been a bit chubby, but I really started to gain weight after moving to the UK in 2006 to work as a doctor. In 2020 I had risen to 24th place. At six feet tall, this put my BMI at 47 (over 30 is obese).

I did diet, but found it difficult to count calories and had no willpower.

The impact of Covid in March 2020 was the turning point. As a man in his 40s with high blood pressure, I was at greater risk for serious complications. I knew something had to change – and I knew I needed something dramatic to get going.

With access to health care limited due to the pandemic, I researched options on my own before deciding on the daily self-administered weight loss shot, 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 realized I needed a plan for a sustainable, long-term healthy life, 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. Here, you eat no more than 800 calories a day, before switching to a moderate low-carb, Mediterranean diet two days a week. rich in protein, fiber and healthy fats, and according to a tailor-made training plan. I realized this was what I needed in collaboration with Saxenda.

I started the injections in February 2021 and they took effect quite quickly, suppressing my hunger. I also followed the new diet: cooking everything from scratch, strictly controlled portion sizes, using a kitchen scale for the first time, and exercising for 30 minutes a day. The results were dramatic: I lost a stone and a half in a month! Within a few months my shirt size went from XXXL to L.

After five months I stopped Saxenda and moved on to the Fast 800. Today, 10th lighter, I feel so much fitter.

So why didn’t my willpower fail this time? Well, I’m empowered by the knowledge that I’ve lost weight by living healthy. Most importantly, I no longer need food to feel better. I just think of it as fuel.

Injectable weight loss drugs are a game changer, but they are not a panacea.

Once I stopped taking Saxenda, the weight would have piled back on if I hadn’t addressed my unhealthy lifestyle. There is no point in getting the injections without a structured approach to healthy living. No medicine in the world can solve that problem.

INTERVIEW: ANGELA ESTEIN