Wegovy, Ozempic, and a watershed for weight-loss drugs?

The compound had first caught the attention of scientists around 15 years earlier when they noticed that French factory workers who used it to make explosives during the First World War lost weight.

It turned out that DNP stimulated the metabolism to burn through the body’s fat and carbohydrate stores, increasing calorie expenditure by 50 per cent.

A study published by Stanford University researchers in 1933 reported that some participants lost more than three Ibs per week without altering their diet.

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Within a year, tens of thousands of Americans were buying the drug in high street pharmacies without prescription or supervision.

Inevitably, it was too good to be true.

The same chemical reactions which accelerated metabolism to promote weight loss also dysregulated the body’s temperature controls, causing users to dangerously overheat.

One unfortunate man who overdosed was said to have “cooked to death”.

Other side effects included cataracts, nerve malfunction, liver poisoning, and life-threatening reductions in white blood cell counts.

By 1938 it was designated “extremely dangerous and not fit for human consumption”. Nonetheless, it continued to be traded on the black market and, latterly, via the internet, especially to bodybuilders.

By 2035, more than half the world's population is expected to be overweight or obese (Image: PA)

The DNL experience is one that has been repeated time and again over the past century.

Few medications have been more blighted by false dawns and health scares than the quest for a miracle weight loss pill.

Amphetamines exploded in popularity in the 1950s and 60s but were eventually banned as a weight-loss aid when it became clear that they were also highly addictive.

In 1972, Aminorex - an amphetamine-like appetite suppressant prescribed in Europe - was pulled from the market when it was found to cause pulmonary hypertension in around one in 500 patients, and was linked to dozens of deaths in Switzerland.

In the 1990s, “fen-phen” (a diet pill combining fenfluramine and phentermine) was engulfed in lawsuits by patients who had suffered heart valve damage, and in 2008, Accomplia (known generically as rimonabant) was rejected by regulators amid concerns that it increased suicidal thoughts.

Yet the demand for a medical remedy for obesity continues to grow.

If current trends prevail, 51 per cent of the world’s population will be overweight or obese by 2035.

Against this backdrop, there is growing excitement that we appear - finally - to have a weight-loss drug that works.

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On Wednesday, NICE confirmed that semaglutide 2.4mg (known by the brand name Wegovy) can be made available on prescription on the NHS in England to patients with a body mass index of 30-plus and at least one weight-related condition.

The Scottish Medicines Consortium has not yet issued its guidance for NHS Scotland, but a decision is anticipated in Spring.

The drug, which patients self-administer by injection once a week, has been described as “approaching the efficacy of bariatric surgery”.

In a clinical trial, more than half of participants lost more than 15% of their bodyweight and one in three lost more than 20% when the drug was - crucially - taken in combination with increased exercise and a reduced calorie intake.

The drug mimics the action of a gut hormone called GLP-1, which is released after eating.

It slows down the movement of food in the gut, sending ‘full’ signals to the brain for longer.

Its potential as a weight loss drug was first discovered in the 1990s when researchers at Danish pharmaceutical giant Novo Nordisk were developing a GLP-1-based drug for diabetes, and noticed that their laboratory mice were getting thinner.

In 2014, Novo Nordisk’s first anti-obesity drug based on GLP-1, Saxenda (liraglutide), was approved by regulators.

However, it required daily injections and patients typically lost just 5% of their bodyweight.

Billionaire Elon Musk is among the US celebrities who have spoken publicly about losing weight using Wegovy (Image: Getty)

Diabetes drug, Ozempic, followed - containing between 0.5-2mg of semaglutide (another synthetic, GLP-1-like molecule), but is specifically licensed as a non-insulin treatment to help diabetics control blood sugar levels.

In 2021, US regulators were the first to approve Wegovy for obesity.

Since then, Novo Nordisk’s share price has doubled and competitors have been scrambling to catch up.

Pfizer is working on its own GLP-1-based drug, while Eli Lilly recently reported that two thirds of participants in a trial for its version of the hormone treatment, Tirzepatide, lost 20% of their bodyweight.

Is the tide finally turning, then, on weight loss drugs?

Wegovy has been described as a “game-changer” - but it is not a cure for obesity.

The current NICE guidelines also come with limitations: it can be prescribed only where patients are also attending NHS weight management services (which are under-resourced and unavailable in some areas, leading to fears of a postcode lottery and lengthy waiting lists), and for a maximum of two years -mirroring the duration of the clinical trial.

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Critics have warned that the latter is “completely illogical” from a clinical point of view, noting that such arbitrary cut-offs are not imposed on other chronic conditions such as high blood pressure.

Evidence also shows that once people stop taking Wegovy, their appetite returns, and they quickly regain Ibs.

This partly reflects an evolutionary quirk that scientists do yet not fully understand.

For some reason, once obese, the human body becomes primed to push back against, and reverse, weight loss.

Untangling this mechanism - and finding a way to stop it - could offer a longer-term solution to obesity.