As another weight-loss drug was this week approved in the US, adding to the tsunami of demand for the medicines, there is concern that that frenzy could result in a return to an era when thinness and weight loss were unquestioningly valued, creating further health issues, writes MedicalBrief.
The Food and Drug Administration gave the go-ahead this week for an obesity drug from Eli Lilly that will be a direct competitor to Novo Nordisk’s hugely popular Wegovy, and follows the runaway success of Ozempic for weigh-loss.
Following a trial which saw patients lose an average 18% of their body weight, compared with Wegovy’s 15%, the drug, tirzepatide, which will be sold under the name Zepbound.
The New York Times reports that the FDA has approved Zepbound for people with obesity and for those who are overweight and have at least one obesity-related condition.
Tirzepatide is already approved for diabetes under the brand name Mounjaro where it competes with Novo Nordisk’s diabetes drug semaglutide, known as Ozempic. But until now, Wegovy – also semaglutide but with a higher maximum dose than Ozempic – was the only approved drug that could safely elicit substantial weight loss in people with obesity alone.
Side effects with Zepbound, similar to those with Wegovy, Ozempic and Mounjaro, are mostly gastrointestinal, like nausea and diarrhoea. Most patients tolerated or overcame them.
Susan Yanovski, co-director of the office of obesity research at the National Institute of Diabetes and Digestive and Kidney Diseases, said: “Just a few years ago it would have been difficult to imagine two medications like semaglutide and tirzepatide leading to the kind of weight loss that previously was only seen when people had bariatric surgery.”
The approval comes at a time when Novo Nordisk is unable to produce enough Wegovy to satisfy the huge demand for the drug. Tirzepatide, which patients take by a self-administered injection once a week, as they do with Wegovy, could ease those shortages.
Competition could also result in lower net prices for both drugs, or how much payers actually spend on them. The prices are high for Wegovy – with a list price up to $1 349 every four weeks in one recent analysis, and a net price around $700.
Zepbound is starting with a list price of around $1 060, according to Eli Lilly.
Development of Zepbound began in 2017 with a small study involving 300 people with type 2 diabetes. After three months, many lost at least 13% of their body weight.
Eli Lilly presented the data at a diabetes meeting in Germany. Some in the audience gasped.
Then came a large 72-week study sponsored by Eli Lilly of tirzepatide in 2 539 people with obesity.
In a packed room at a meeting of the American Diabetes Association last year, the study’s principal investigator, Dr Ania Jastreboff of Yale, revealed the results. More than half the patients receiving the highest dose lost at least 20% of their body weight. No drug has ever before shown such a profound weight loss.
For Eli Lilly, the results were a culmination of research that began a decade ago. But like Novo Nordisk, the company was trying to produce a new diabetes drug.
“Obesity wasn’t a main focus for us,” Dr Daniel Skovronsky, the chief scientific and medical officer at Eli Lilly, said, adding that “it was not seen as a commercial opportunity”.
The sad history of weight loss drugs was a lesson, he thought. “There had never been a successful obesity drug,” he said, “and previous drugs didn’t cause enough weight loss to have an impact on peoples’ health.”
Suddenly, Eli Lilly’s opinion of studying weight loss changed.
“We thought: ‘This medicine can change the world,’” Skovronsky said. “We said: ‘This is the one. This is our priority.’”
But Zepbound is only the beginning for Eli Lilly. The company and other pharmaceutical manufacturers are working on drugs that could be even more powerful.
The next Lilly drug adds glucagon, another gut hormone, to the two in Zepbound. It apparently stimulates metabolism and draws fat out of the liver.
And, like Novo Nordisk and other companies, Eli Lilly is working on a pill form of tirzepatide. It is undergoing clinical testing.
TIME reports that prescriptions for these weight-loss meds are up 300% since early 2020, with more than 9m written in America in the past three months of 2022 alone.
Demand is so great that Ozempic, Wegovy and Mounjaro have all recently gone into shortage, and patients with type 2 diabetes have, in some cases struggled to fill their prescriptions as they compete for limited supplies with people looking to slim down; meanwhile, spas, internet suppliers, and compounding pharmacies are all fighting for their piece of the Ozempic pie.
No one can quite agree on whether this frenzy is a good thing. Plenty of physicians (and, of course, the pharmaceutical executives who stand to get very rich) say it is, given that roughly three-quarters of US adults are either overweight or obese and thus, say public-health authorities, risk various serious health complications.
But some doctors, researchers, and activists are uneasy about living in the age of Ozempic.
Before the Ozempic tsunami, a growing number of doctors and researchers had begun advocating for Health at Every Size, a research-backed set of principles from the Association for Size Diversity and Health that hold body size is not a measure of health or worth, and that all people deserve high-quality, non-stigmatising medical care;'.
Their efforts contributed to a burgeoning field known as “weight-neutral” medicine, which sees “weight” and “health” as separate, and worked in tandem with the wider body-positivity movement to help loosen the diet industry’s vice-like grip on American psyches.
As the 2000s progressed, women’s magazines stopped pushing diets quite so hard. Clothing brands bragged about hiring larger models. Even Weight Watchers rebranded as a “wellness” company called WW.
Then Ozempic and its cohort came along, and it turned out lots of people still wanted to be skinny. Some industry watchers have even predicted that the rise of drugs like Ozempic – and an impending crop of new, potentially more effective, competitors including Eli Lilly's newly approved offering, Zepbound – could spell the end of obesity.
But as these drugs transform both standard medical practice and cultural ideas about weight loss, a contentious debate is simmering beneath the surface: should we even be treating obesity?
The medical establishment is clear about its stance on obesity: it is a “common, serious, and costly chronic disease”, as the US Centres for Disease Control and Prevention puts it.
If obesity is a disease, it follows logically that it should be treated. Historically, diet and exercise have been plan A for treating obesity. But in practice, lifestyle changes like these often aren’t enough.
“Try as we might, a lot of exercise typically does not result in a significant amount of weight loss,” says Glenn Gaesser, a professor of exercise physiology at Arizona State University.
And then came Ozempic and the rest. Ozempic, Wegovy, and Mounjaro work by simultaneously slowing digestion and mimicking the appetite-suppressing hormone GLP-1 through a weekly injection. (Mounjaro also targets a second type of hormone receptor.)
This double whammy means people need to eat far less than usual, leading to an average 15% to 20% reduction in body weight after about a year. They don’t work well for everyone, but compared with older meds, the efficacy of these drugs is remarkable, the weight loss undeniable.
And this class of drugs doesn’t just lower the readings on a scale. According to data from Novo Nordisk, semaglutide (the generic name for both Ozempic and Wegovy) slashes the risk for major cardiovascular events like heart attack and stroke by 20% among overweight or obese adults with heart disease.
Obesity tools
“We have effective tools” for weight loss now, says Dr Laura Davisson, director of medical weight management at West Virginia University Medicine. “Why not use them?”
There is one big reason, according to a passionate group of doctors, researchers, and activists who believe in the principles of Health at Every Size. They feel obesity never should have been labelled a disease in the first place – and thus may not need to be treated at all.
“Manipulating weight is not a path to health,” says Ragen Chastain, a certified patient advocate who co-authored a library of Health at Every Size resources. “The belief that fewer fat people existing is good – that’s weight stigma.”
As Chastain and others like her see it, Ozempic and its sister drugs are not life-saving anti-obesity medications, but new tools for reinforcing old, damaging body standards rooted in stigma, not science, while raking in billions for pharmaceutical companies.
The idea that obesity is not a disease is still a controversial take in mainstream medicine.
The CDC and American Medical Association (AMA) disagree with it, as do many physicians in the field.
“‘Healthy at any size’ – I don’t even like the connotation,” says Dr Caroline Apovian, co-director of the Centre for Weight Management and Wellness at Boston’s Brigham and Women’s Hospital. “There is unhealthy body weight.”
And yet, the research on weight and health leaves room for questions. Plenty of studies show links between obesity and health problems, ranging from fatty liver and sleep apnoea to heart disease and cancer.
But studies also suggest that up to half of people with obesity are metabolically healthy, not at elevated risk for heart disease and death, and that overweight people may in fact have a lower risk of premature death than people at “normal” weight.
Studies have also found that, even though obesity is considered a risk factor for developing heart disease, overweight patients tend to fare better than thinner patients when they’re treated for related conditions, a finding often called the “obesity paradox”.
Research also suggests weight loss has less of an impact on health than physical fitness or the quality of one’s diet.
“We’ve got this entire body of research based on a hypothesis that if you make fat people look like thin people they’ll have the same health outcomes,” Chastain says. But she’s not convinced that’s the case at all.
For one thing, body mass index (BMI), the measure commonly used to diagnose overweight and obesity, is inherently flawed, a fact acknowledged by influential organisations including the AMA.
When the AMA designated obesity a disease in 2013, its own Council on Science and Public Health urged against that decision. The council’s chief concern was the imprecision of BMI, which is a crude measure of total weight relative to height that, on its own, does not say much at all about someone’s health.
Today, experts widely agree BMI is imperfect. And yet, it’s still used in research, to diagnose obesity, and to determine who is eligible for drugs like Wegovy.
Dr Lisa Erlanger, a family-medicine physician who supports Health at Every Size, believes weight functions less as a measure of health than as a social determinant of health – in other words, a non-medical factor that nonetheless affects health through its impact on overall wellness. The weight stigma larger people encounter in doctor’s offices, the workplace, and social settings can all harm health, she says.
Sky high demand
Some industry watchers have predicted Mounjaro will become one of the highest-selling drugs of all time. Meanwhile, Ozempic and Wegovy helped Novo Nordisk reach a nearly $442bn market capitalisation by late October – higher than the gross domestic product of its entire home country, Denmark.
It’s no surprise, then, that an army of new weight-loss medications are receiving or marching toward regulatory approval, some with results even more impressive than their predecessors.
Pharma giants are also exploring oral GLP-1 drugs, which would have an even lower barrier to entry than their injectable formulas. (Novo Nordisk’s Rybelsus is already available as a pill.) With so many options currently or soon to be available, it’s not so far-fetched to imagine a world when all anyone needs to lose weight is a prescription.
The New York Times – F.D.A. Approves New Obesity Drug That Will Compete With Wegovy
TIME article – Should We End Obesity? Open access)
See more from MedicalBrief archives:
Obesity-linked deaths in US triple since 1999
The mystery behind new obesity drugs
Obesity should be treated as urgent ‘gateway’ medical condition, say experts
Obesity drugs may be added to WHO’s essential medicines list