Expect a bumper year for weight-loss drugs

FOR decades, weight-loss drugs have been a disappointment, delivering ineffective or even dangerous treatments. The recent arrival of drugs that are both effective and safe is therefore a medical milestone. Some now talk of a long-term future in which obesity might be cured. That is no small claim: obesity is a serious global problem, with 1.1bn people, or roughly 14% of the world’s population, being obese.

In 2024 the two companies, Novo Nordisk and Eli Lilly, will battle for dominance of what could be a $77bn market by 2030. Their drugs Wegovy (semaglutide) and Mounjaro (tirzepatide) are going to be blockbusters. The size of the market is attracting a lot of competition and innovation. More than 70 other obesity treatments are in development, according to STAT, a medical news site. Most firms are chasing the same idea, namely glucagon-like peptide 1 (GLP-1) agonists. These mimic the hormones the body produces after a meal, thus regulating glucose in the blood, which is why GLP-1 drugs worked so well to treat diabetes.

Unexpectedly, though, GLP-1 drugs also work on weight loss. They do this by slowing down the rate of “gastric emptying”, keeping people fuller for longer. They also affect the brain’s hypothalamus, which controls hunger. And they seem to make fat more likely to break down. Although GLP-1 will probably continue to be the primary target for new medications, some firms are exploring additional cellular targets in the hope of making ever more effective drugs that shed ever higher percentages of body fat.

Ray Stevens, the boss of Structure Therapeutics, says the challenge is to ensure patients tolerate the medicine and find it easy to use. A number of firms, including his, are chasing oral versions of GLP-1 drugs. They are betting that oral drugs will be cheaper to make and deliver, and will be more tolerated by patients, who don’t like injecting themselves. Novo Nordisk hopes to deliver a new oral version of semaglutide as early as 2024.

The drugs have proved so popular that demand has continually exceeded supply. Supply is likely to improve in 2024, but shortages of the medications are expected to continue. GLP-1 drugs are generally regarded as safe but there are risks of gastrointestinal complications such as pancreatitis and bowel obstructions. Another quibble is durability. The drugs have to be taken continuously to keep weight off. Amgen, which is developing a longer-lasting drug, will get results from phase-2 trials in the coming year.

Human trials may also start in 2024 on a one-time gene-therapy GLP-1 drug, which triggered a 23% weight loss in obese mice. Biotech Fractyl Health, based in Lexington, Massachusetts, injected the drug into the pancreas, allowing mice to make their own GLP-1 agonists. This sort of research will need many years of work before it is deemed safe and effective in humans. Gene therapy also poses the challenge that, unlike with a medication, patients cannot stop taking it if there are unwanted side-effects.

One factor driving interest from doctors is that obesity is increasingly seen as a medical, rather than cosmetic, concern. A recent paper on Wegovy showed that it can reduce the risk of major cardiovascular events, such as strokes and heart attacks, by 20%. Given widely, weight-loss injections in America could prevent hundreds of thousands of heart failures. Globally, such drugs could transform public health. In 2024, more data on the health impacts of obesity medicines will bolster the case for prescribing these drugs.

Ahmed Ahmed, a reader in metabolic surgery at Imperial College London, says he expects a flurry of consumer interest in nutraceuticals, such as konjac fibres, that enhance or amplify the body’s own gut-peptide systems. Those who have been lucky enough to be able to get hold of prescription GLP1 drugs are, says Mr Ahmed, “reasonably happy with them, as long as they don’t expect too much weight loss”. The catch, though, is that you have to keep taking them. He says one patient has likened the psychological need to take the drug to an opiate addiction. But eventually, taking a cheap oral drug every day may become widely accepted. For now, the revolution is just beginning. ■

Natasha Loder, Health editor, The Economist