The Astonishing Rise of Ozempic: A 21st Century Medical Phenomenon

How and why did an injectable medication intended for diabetics become the medical phenomenon of the 21st century, hailed as a discovery perhaps even more dramatically important than last century’s breakthrough drug, penicillin? The surprising, short answer is that its side effects have turned out to be at least as significant as its ability to moderate blood sugar levels. But the spectacular rise of Danish pharma giant Novo Nordisk’s Ozempic, the pioneering diabetes drug that targets the GLP-1 (glucagon-like peptide 1) gut hormone, is primarily due to its ability to spur dramatic and sustained weight loss. So attention-grabbing and popular was that one feature that just one year after Novo Nordisk released Wegovy, its Ozempic spin-off explicitly for weight loss, it was struggling to keep up with international demand. Behind that sudden success lies a 40-year development saga full of unexpected twists and turns, near-misses, frustrations, triumphs and, above all, dramatic scientific insights and breakthroughs. Ozempic was the outcome of inspired work by a handful of people who believed this kind of obesity-fighting drug could change lives and alter worrying global public health trajectories. All these strands come together in this timely book by Galway-based Reuters journalist Aimee Donnellan. As she notes in Off the Scales: the Inside Story of Ozempic and the Race to Cure Obesity, obesity – defined as a body mass index (BMI) of 30 or higher – produces “deadly offshoots” such as diabetes, stroke and heart disease. “Experts in the field say obesity may not appear on a death certificate, but it is responsible for hundreds of other deadly conditions,” she writes. Ozempic debuts at a point where the EU was spending €70 billion annually on the condition, while in the UK, obesity and its directly related illnesses were sucking up 5 per cent of the total NHS budget. The United States, where a higher percentage of the population is obese, was spending at least $150 billion a year treating it, with another $66 billion in lost productivity. Perhaps that’s far too modest – in 2016, US think tank the Milken Institute estimated that treating obesity cost US taxpayers $1.4 trillion annually, seven times the outlay for cancer and dwarfing “all other diseases”, says Donnellan. Yet even as obesity rates rose every decade from the 1970s onwards, at about a percentage point per year, pharmaceutical companies apparently didn’t see the disease as a significant market for drug development. One of Donnellan’s dumbfounding revelations – among so, so many – is how medical research institutions, and Novo Nordisk too, kept brushing off the conviction of so many coalface researchers that the real (and vast) breakthrough opportunity for a GLP-1 medication was in treating obesity. The evidence certainly seemed clear and irrefutable. In 1990, the US national obesity rate ran at 11 per cent, with no US state at 20 per cent. By 2010, every state had obesity rates above 20 per cent. Between 2017 and 2020, obesity hit 41.9 per cent in the US, according to CDC (US Centers for Disease Control and Prevention) figures. Another quarter of the US population is overweight. Ozempic ultimately emerged from what was practically a covert skunk works operation within Novo Nordisk in the mid-1990s. One manager, Mads Krogsgaard Thomsen, and a brilliant company scientist, Lotte Bjerre Knudsen, teamed to create an effective GLP-1 drug that would target obesity, not just diabetes. When higher-ups pulled Thomsen’s funding for the project, he used his own small discretionary budget to quietly keep Knudsen and her team going. They in turn were building on a major discovery in the 1980s by another woman, the Macedonian-born chemist Svetlana Mojsov, who arrived in New York in 1972 as a 25-year-old eager to apply her razor-sharp mind to a physical chemistry PhD at Rockefeller University. Advised by her mentor to choose a topic that deeply interested her, she decided to explore how the body controls blood sugar, focusing on the gut hormone glucagon, which raised blood sugar. Perhaps, she posited, it could be harnessed in a way that would offer diabetics a better alternative to insulin, which was effective at blood sugar control, but carried risks and required daily injections. Donnellan profiles several men – Joel Habener, Daniel Drucker and Jens Jul Holst – also involved in proving glucagon could potentially become that alternative. But it is Mojsov she credits as the steely linchpin in unravelling the secrets of GLP-1. Mojsov works tirelessly to overcome significant scientific challenges in an environment full of sexist dismissiveness and exploitation. When it emerges that she has not been included on the valuable patents for GLP-1, she fights back with a successful legal action and was subsequently listed on five patents for a discovery that, Donnellan observes, may one day garner a Nobel Prize. Fortunately, on the advice of her mentor, Mojsov had kept detailed notebooks on her work that proved her contributions. The book ends with her finally being recognised in 2024, alongside Habener and Knudsen, as a co-discoverer of GLP-1. This detailed look at the long journey that leads to GLP-1 drugs such as Ozempic, bolstered by an insider look at the world of commercial drug development and marketing, makes for a lively and eye-opening tale. It’s sobering to realise from these pages how much the success of a medication can rest on its US advertising budget and in Ozempic’s case, a jaunty earworm jingle (in the US, unlike Europe, prescription medications can be marketed directly, and relentlessly, to consumers). But Donnellan wisely and insightfully broadens her consideration by placing the development of these new weight-loss drugs in a necessary and complicating social and moral context. Obesity carries much societal baggage. It’s one of the few diseases for which the patient is routinely blamed and shamed, even by much of the medical profession, despite decades of studies establishing genetic, environmental and social causes. Donnellan shows how many, including some Novo Nordisk executives, saw diabetes as a disease worth targeting, while obesity was viewed as the result of poor personal choices and a weak will. But it’s now known that many people have a genetic disposition to store more body fat, and lack an appetite regulator – beneficial for our ancient hominid ancestors but not in today’s calorie-saturated world. Add in a food industry churning out highly processed foods full of addictive and tasty fats and sugars in ever larger portions – and one which needs to keep people eating to enhance profits. Ready meals have become a helpful but typically calorie-laden solution for time-poor and income-poor working adults. Meanwhile, as adults and, increasingly, children wrestle with a relentlessly food-imbued environment, popular culture has long presented thinness as a norm. And just as a body-positivity movement had begun to provide a more realistic counter-picture, along comes this new wave of weight-loss medications. Their high cost also creates inequalities. These medications hold much promise, but also raise significant issues. As an effective way of investigating them, Donnellan offers the stories of a number of GLP-1 users to give insight – at times, utterly heartbreaking – into the experience of living with obesity and the discrimination, prejudice, bullying and mental health challenges that can go with it. For many of them, GLP-1 medications such as Ozempic, Wegovy and Mounjaro can be life-altering. Blood sugar rebalances, inflammation and pain decreases, new opportunities open up. But there are costs. One woman grows despondent at realising how her new thinner shape alone seems to have made her suddenly visible and promotable at work. Some users experience side effects including severe nausea, vomiting and gastrointestinal upset. In one of the rare cases documented by Donnellan, people have been left permanently afflicted even after coming off these medications. But the popularity and attractiveness of what Hollywood calls “Vitamin O” as a weight-loss tool seems undimmable. Already, says Donnellan, GLP-1 seems to be reshaping the world. For the first time in decades, obesity rates have dropped – only slightly, but that’s after years of relentless increase. Food and drinks companies, restaurants and even casinos are reportedly trying to figure out how to survive in a lower-appetite landscape in which GLP-1 seems to reduce the desire to eat out, drink alcohol or gamble. Tomorrow’s world may be one in which pressures on national health budgets are eased, risks lower for many serious illnesses, and mental health improves. Or, on the other hand, perhaps shallow beauty ideals may become more embedded, a health divide based on income could solidify further, and undesirable health impacts from long-term GLP-1 use – not yet understood, as the drugs are so new – could arise. Donnellan says that when current patents expire, competition in the years ahead will bring “cheaper, better, and more accessible weight loss treatments”. With ever more evidence showing that GLP-1 medications can help treat a growing roster of illnesses, it’s conceivable that we may all one day be taking them. Like it or not, Ozempic has successfully whetted appetites for the next course. Further reading The Mould in Dr. Florey’s Coat: The Story of the Penicillin Miracle (Abacus, 2005) by Eric Lax. Considered one of the best histories about the fortuitous and casual discovery of a drug so important that it was classified an Allied weapon of war during WWII for its ability to prevent fatal wound infections Empire of Pain: The Secret History of the Sackler Dynasty (Picador, 2022) by Patrick Radden Keefe. The darker side of Big Pharma. A disturbing exposure of how a devastating societal fallout — the opioid crisis — has resulted from the greed and avarice of a powerful family pursuing markets for its painkillers