Loss leaders

Since 2021, the world has been on a losing streak. Following the approval of the diabetes drug semaglutide as a weight-loss treatment, anti-obesity medicines have become one of the most used drugs with estimates that around 12% of adults have taken them in the US alone. In 2023, Science named these GLP-1 agonist drugs its breakthrough of the year.

Obesity is a significant societal problem, now estimated to affect over a billion people. Its impact on patients is immense, leading to complications such as diabetes and cardiovascular problems, which in turn puts strains on health services. It’s a complicated disease that has genetic, environmental and physiological factors as well as societal and structural ones such as the availability and affordability of healthy food; obesity is more likely to affect those in low socioeconomic groups, for example. A drug that can help cut weight will not only improve and save lives, it will have an impact on all of society.

After decades of failures and false starts, the breakthrough finally happened with semaglutide – a mimic of the hormone glucagon-like peptide-1. GLP-1 controls insulin levels and appetite via GLP-1 receptors in the pancreas and brain, and the first drugs to target GLP-1 receptors were approved in 2005 as treatments for diabetes. But as trials for these diabetes drugs also showed weight loss in their cohorts, there were hints that this could be a way to tackle obesity. After many years of development, semaglutide hit the headlines in 2021 with trial results showing a 15% reduction in weight, tipping the scales enough that many type 2 diabetes patients go into remission.

Those sorts of changes are achievable through lifestyle changes alone, but that can be harder to sustain. Participants in a recent study lost 10–15% of their weight over one year on a calorie-controlled ‘soup and shake’ diet that starts with three months on just 800kcal per day. By comparison, participants on the semaglutide trial had to cut their normal calorie intake by 500kcal. Around 55% of people completed the soup and shake trial, compared to 80% on the semaglutide trial. It’s not hard to see why semaglutide has the edge.

Last year, semaglutide sales made its owner, the Danish drug maker Novo Nordisk, Europe’s most valuable company and economists have suggested that Novo’s success alone was enough to lift the Danish economy to a couple of percentage points of growth in 2023. The drugs are so popular that the manufacturers cannot make them fast enough. As our recent story explains, makers are on a spending spree to buy or build new capacity, betting billions of dollars that these drugs will be generating revenue for many years to come.

Other pharma companies are also eager to get a piece of the action, creating the kind of blockbuster gold rush that can define the sector’s course for a generation. Yet even with rivals coming fast, the investment bets look sound: recent trials also show promising results for heart and kidney diseases. This may only be the beginning.

Their impact is already going beyond the scientific. Weight-loss drugs were blamed for investor panic that saw Pepsi’s share value dropping 17% over three months last year, and Weight Watchers has also seen its shares slump. US supermarket chain Walmart has noted that shoppers who use GLP-1 drugs buy less food. And endorsements from the likes of Elon Musk have made them celebrity drugs, driving demand among the weight-conscious wealthy.

Yet for those who most need these drugs, there are still problems. The drugs are expensive for one, and they are only truly effective if they are accompanied by supported, sustainable lifestyle changes. Obesity carries a social stigma and despite all we know about the pathology of obesity many still view it in simplistic terms that puts the blame on individuals. If GLP-1 drugs can help us lose those unhelpful attitudes and obesity’s structural issues, then may our losing streak continue.