Off the Scales by Aimee Donnellan The Inside Story of Ozempic and the Race to Cure Obesity
What's it about?
Off the Scales (2026) explores the decades-long global race to create a long-lasting version of the GLP-1 drug semaglutide to help fight the growing diabetes and obesity epidemics. Presenting all sides of the story, from the fraught scientific competition to be the first to bring these drugs to market, to the side effects rippling through global societies, it uncovers.
Skinny is in. Around the world, waistlines are shrinking as millions upon millions inject a once-weekly drug. Designed to control blood sugar for those with Type 2 diabetes, it was found to have remarkable weight-loss benefits. Soon, diabetics had difficulty getting their prescriptions filled because demand for the drug was so strong that manufacturing couldn’t keep up with demand.
The molecule known as semaglutide is being touted as a miracle drug. Sold under brand names like Ozempic or Wegovy, it has begun to reshape societies. While this success might appear to have come overnight, the search for a better treatment for blood sugar management actually started decades ago, with the pioneering efforts of biochemists on two sides of the Atlantic. This lesson dives deep into the story of the creation of these drugs, their promise and benefits. But it also tackles the less glamorous side of weight-loss miracles: the serious side effects and negative impacts of treating obesity in an increasingly overweight world. Whether you’re curious about the “jab” that everyone is talking about, or want to know more about a treatment that is already changing your life, this lesson is for you.
According to the World Health Organization, between 1976 and 2006 the proportion of obese adults in the US population rose exponentially, to around thirty percent and rising. This number counts only those whose Body Mass Index, or BMI, is above 30. It does not include adults who are just overweight, or whose BMI is between 25 and 30. In 2023 the Centers for Disease Control in the US estimated the number of overweight or obese adults nationally totalled more than 70 percent.
The trend reveals a lot about changes to society since the 1980s, the decade when the steepest climb in obesity rates began. But it also hides behind charts and numbers the real costs of increasing waistlines on individuals and communities. For instance, many obese individuals dread going to the doctor. Every health complaint, pain, or symptom they bring to their appointment is met with the same response: just lose weight. Obesity has been seen as a failure of willpower and self-control for decades, and the cause has always been assumed to be a flaw in character, not genetics or biochemistry. The result?
Increasing numbers of overweight or obese people avoided doctors, who peddled the same tired advice decade after decade: eat less, exercise more, you’ll lose weight. Patients who tried found themselves on a diet roller coaster that often saw them gaining more in the end. Others turned to surgeries, radical programs or intensive interventions that had serious consequences for their health. Meanwhile, the public belief that excess weight comes only from gluttony means patients who fail to lose weight face a life full of judgement from even the most well-meaning people in their lives. Like a cloak of shame, the excess weight is more than just a physical burden weakening joints and straining organ systems. It is the weight of harsh judgement.
No wonder so many carrying extra weight turn to larger potions or sweet treats for comfort, perpetuating an escalating, vicious cycle. And adults are not the only ones carrying the load. Children’s weight has seen a similar rise in recent decades. Rates of overweight and obese children had tripled, to around thirty percent, when First Lady Michelle Obama kicked off the Let’s Move initiative in 2010.
The goal was to cure the obesity epidemic in a generation. But even the Obamas understood there was no quick fix, and the program didn’t slow the growing crisis. Likely because there was an entire commercial food system keeping the weight gain rolling.
Individuals bear the burden of excess weight and obesity, along with the Type 2 diabetes, high blood pressure or heart disease that often accompany it. But the causes of obesity are far more collective. Social and cultural factors, governmental legislation, corporations and lobbyists all conspire to create the perfect conditions to produce obesity on a global scale. Starting in the 1980s, there was an intentional effort on the part of large brands like Kelloggs and Kraft to embrace the trend of abundance in their marketing efforts.
With the rise of households in which both parents worked, and the widespread adoption of the microwave oven, industrial food producers recognized the growing need for convenience foods. Households had less and less time to cook meals from scratch. Food companies soon realized that they could make far more money selling ultra-high processed foods, like microwave meals and packaged snacks. By just 1994 the US Department of Agriculture’s estimate of food advertising spending reached 36 billion dollars a year. This money was spent entirely on the effort to get Americans to eat more. It played up any nutritional benefits, like added vitamins and minerals, while never mentioning the added sugar, salt, stabilizers, preservatives, emulsifiers, and coloring.
Meanwhile, soft drink companies, like Coca-Cola and Pepsi, were spending billions on lobbying to stay available in schools. Food companies redesigned their highly processed breakfast cereal boxes with cartoon characters in bright colors to appeal directly to kids. These characters appeared relentlessly in ads aired during children’s television programs. Yet one serving of Smacks, a sweetened puffed-wheat cereal, contains as much sugar as a Snickers bar. Fast food companies also responded to this demand for quick meal options and abundance by increasing the portions of food items. By 2002, for instance, the “large” size of McDonald’s french fries was equivalent to one that was considered “supersized” in 1998.
Over the same decades, other aspects of life were also changing. More people working meant that most adults had little time for pursuing sports, recreation, or hobbies. Program cuts and less physical education in schools made sedentary lifestyles seem normal. Economic shifts left entire neighborhoods as food deserts, or those in which only fast or processed food options were available. So while individuals are judged for the eating choices that led to weight gain, there is a global system driving obesity across all levels of society. Fortunately, efforts were already underway in an obscure area of science that held the promise of a solution.
When Svetlana Mojsov stepped off a plane at JFK Airport in 1972, she was coming to New York to pursue her PhD in biochemistry fresh from the University of Belgrade. She’d learned about Rockefeller University, a private postgraduate institution for biochemical research in New York, from a former professor who’d taken a sabbatical at Columbia University. Young and full of optimism for her future, she was eager to make her mark in research. Raised in the former Yugoslavia, she was astonished at the portion sizes in America.
Having rarely seen meat growing up, the average T-bone steak served in New York restaurants was more meat than she’d seen in her lifetime. She couldn’t remember seeing an obese person growing up, but she saw many on her campus at Rockefeller University participating as research subjects. That’s because to a growing number of researchers, the idea that obesity was only about willpower was simplistic at best. More were coming to see obesity as a disease that could be treated. Laboratory research with mice had proven that hormones like leptin helped some animals feel full with less food, keeping them slim. If appetite was controlled by hormones, then hormones could hold the key for weight loss.
As far back as 1976, researchers like Jens Juul Holst at the University of Copenhagen, were attending international biomedical conferences discussing the possibility of unknown gut hormones controlling appetite and overall health. But there was still considerable mystery around what caused some to gain while others stayed slim on similar diets. They were also faced with the exponential rise in Type 2 diabetes cases that shadowed the rise in obesity. Insulin, the earliest treatment, was harvested from pigs. But the number of diabetes patients had doubled between the 1950s and the 1970s alone. If the diagnoses kept increasing at this rate, pig supply couldn’t keep up with demand.
At Rockefeller University, Mojsov focused on studying glucagon, a hormone discovered back in the 1920s that was shown to affect blood sugar. She hypothesized that if harnessed correctly, it could be used to help treat diabetes. But to do this, she would have to synthesize a chemical version in the laboratory. With necessity as the mother of invention, she set about to do just that, and pioneered a method for synthesizing large quantities of protein molecules, known as peptides, in the process.
This breakthrough both launched Mojsov’s career, and placed her at the forefront of a race on both sides of the Atlantic to synthesize a hormone-based drug that could help control blood sugar. In the decades following Mojsov’s breakthrough in peptide synthesis, research into this area exploded. Mojsov’s synthesized peptides drove research at her new position as an associate in biochemistry at Massachusetts General Hospital.
She was initially hired by Michael Rosenblatt, the head of the endocrinology unit, to synthesize proteins for other researchers. But by the Fall of 1983, she was director of the Peptide Synthesis faculty at Mass General, and appointed an associate of the Howard Hughes Medical Institute. This gave her funding and time to pursue her own research. There she continued her work on glucagon and spent years doing animal studies attempting to establish its forms and effects in animals.
Her former mentor at Rockefeller, Bruce Merrifield, with whom she shared her preliminary results, strongly urged her to document her experiments in laboratory notebooks. Advice that turned out to be essential in years to come. Especially when fellow scientist at Mass General, Joel Habener, heard about her research. Soon a member of Habener’s team, Canadian biochemist Daniel Drucker, approached Mojsov about collaboration. Habener’s lab had identified a glucagon-like molecule in the bellies of fish, dubbed GLP-1, for glucagon-like peptide. Though reluctant to share her process, Mojsov was aware that collaboration could speed up their progress.
In September of 1986, Mojsov and Habener published their first joint paper, identifying GLP-1 in the gut and tracing its active forms. This paper was published in the very same month that Jens Juul Holst in Copenhagen was presenting the same experimental findings at a conference in Italy. Two teams were on the trail of GLP-1 as a potential diabetes treatment, and reaching the same breakthroughs simultaneously. Just a year later, however, Mojsov had a second breakthrough when she used a method pioneered by Gordon Weir, who had discovered a method to monitor insulin in rat pancreases in real time using GLP-1 synthesized by Mojsov. Using Weir’s method, she injected GLP-1 into rat pancreases and was able to confirm its effects. The results were published in 1987 with Mojsov and first author, Weir and Habener as second and third.
Just fifteen years after arriving in New York, she had confirmed GLP-1’s role in releasing insulin. Like so many other women in science both before and after, Mojsov would go on to have to fight for her place in this groundbreaking discovery through protracted lawsuits about patent rights. Her careful documentation of the process meant she eventually received thirty percent of the outsized revenue her discovery garnered. But there was still a long way to go before her pioneering work could result in new treatments. That breakthrough would come from far away and the most unlikely of sources: the belly of a lizard.
Four years after the GLP-1 breakthrough by Mojsov and others in Massachusetts, biochemist John Eng at the Veterans Affairs Medical Center in the Bronx was pursuing similar research into gut hormones. Remembering a paper by a Belgian scientist who noted that the Gila Monster, a lizard living in harsh desert environments, had remarkably stable blood sugar despite eating only a few times a year. In 1990 Eng isolated a molecule in reptile venom that worked very much like GLP-1 but had more long-lasting effects. This was important because with GLP-1’s role confirmed in blood sugar regulation, drug companies faced another problem.
The human body has enzymes that chop up the peptide when it is encountered outside the pancreas. This means that ingesting or injecting GLP-1 is useless. Biochemical researchers around the world were trying to be the first to create a viable GLP-1 drug that would evade the body's defense mechanisms long enough to provide lasting stability for sugar levels Eng’s discovery spurred researchers back in Copenhagen at the headquarters of Novo Nordisk, the European pharmaceutical giant. There, chemist Lotte Bjerre Knudsen was attempting to directly harness Mojsov’s breakthroughs in GLP-1. She had expertise in enzymes, and eventually collaborated with her boss, biochemist Mads Krogsgaard Thomsen, for the research. But they were beaten to the launch by a small San Diego pharmaceutical company in 2005.
John Eng had licensed the Gila Monster compound, which was launched under the name Byetta. Thomsen and Knudsen were devastated, but Byetta had a major drawback: it had to be injected twice daily. They headed back into the laboratory to experiment with similar molecules that needed fewer doses. In 1997, they succeeded in formulating a long-lasting glucagon-like peptide, liraglutide. First tested on rats, liraglutide had remarkable benefits for stabilizing blood sugar. Early studies also showed it caused appetite suppression, meaning the drug had weight loss benefits.
But in 2003 it was shown to cause tumors in the thyroids of test rats. The drug was eventually released when it was proven the tumor mechanism was unique to mice and rats, but this took time, and liraglutide needed to be injected daily. Thomsen, however, had been secretly experimenting with a similar peptide, semaglutide, as well. And that molecule was already exceeding all earlier GLP-1 versions for both stability and effectiveness. It required injection only once a week and showed no tumor risk. It was eventually released as Ozempic and hit the US market in 2018, marking the culmination of almost fifty years of research.
An ad campaign mounted in July of that year touted it as “magic” It certainly appeared that way. Users taking Ozempic to control blood sugar lost 17 to 18 percent of their body weight compared to 2 to 3 percent for dieters. The results also lasted as long as the patient stayed on the drug. Not only could it control blood sugar, semaglutide could also attack the underlying cause of diabetes and fight obesity.
Soon after the launch by Novo Nordisk, other drug companies followed suit with their own versions of GLP-1 agents, like Tirzepatide and Dulaglutide. As manufacturers struggled to keep up with demand, social media began to explode with weight loss stories from those who had struggled their entire lives. Semaglutide drugs began bringing in billions for drug companies, too. The estimated market share for drugs like Ozempic rose to almost 25 billion between 2018 and 2025, with 2026 projected to raise that number to over 28 billion.
With millions of individuals now on these drugs, it was only a matter of time before the news of side effects began appearing Some side effects were quite positive. For instance, Clothilde first heard of Ozempic when she’d seen a new doctor in early 2019. She’d long been discouraged by her excess weight, despite staying active and being careful about her diet. She’d borne the shame of doctors scolding her for any kilo gained, a common practice by doctors in France. This time, however, she left the doctor’s office with a new prescription for a once-a-week injection. Almost from the first dose, she noticed something remarkable: an inner silence.
She’d not realized how much she obsessed all day every day with what she would eat, and when. This voice had buzzed in her head since she was a little girl. Not only did she lose weight, food was no longer at the center of her life. Other patients weren’t so lucky. Some couldn’t get over the initial nausea. Semaglutide essentially slows down digestion and stomach emptying.
Nausea is common and in some cases severe. Others, like Jorge, who’d begun semaglutide after his physician diagnosed him with both obesity and pre-diabietes, had more severe side effects. For a small but significant portion of semaglutide patients, the gut-slowing effect of the medication is powerful. Even at the lowest doses, patients like Jorge had severe nausea from day one, but shedding weight made him continue. Soon, the daily nausea and vomiting was accompanied by terrible gas and stomach cramps. He was found to have developed gastric paresis, or a paralysis in his gut, which was likely permanent.
Similar patients had full or partial colostomies, meaning parts of their gut needed to be removed. For a smaller group of semaglutide users, the risks are even more severe. For people with body dysmorphia, both the hype and the flood of semaglutide drugs into the market has been dangerous. Those chasing more and more distorted views of thinness have driven the black market for semaglutide drugs into a frenzy – many braving the risk of counterfeits to achieve a skinny ideal.
However they risk malnutrition, major organ failure, and ultimately death in this reckless pursuit of thinness. One thing is certain. Just five years after launch, semaglutide and its derivatives are reshaping society. What remains to be seen, is at what cost.
The main takeaway of this lesson to Off the Scales by Aimee Donnellan is that… Though semaglutide drugs like Ozempic or Wegovy might seem to have appeared overnight, they were the result of long-term biochemical research in laboratories around the world. Building on major discoveries on the role of complex protein molecules, known as hormones, scientists in the US and Denmark raced to isolate and synthesize the glucagon-like proteins that help control blood sugar in animals to treat humans. Almost 50 years after glucagon was first synthesized in a laboratory, scientists at Novo Nordisk launched a glucagon-like molecule, semaglutide under the brand name Ozempic. Within months, demand for the drug, which not only controlled blood sugar but served as an appetite suppressant, started to outstrip supply.
In the five years since release, this class of drugs has begun to reshape not only individual waistlines, but the culture at large.
Off the Scales (2026) explores the decades-long global race to create a long-lasting version of the GLP-1 drug semaglutide to help fight the growing diabetes and obesity epidemics. Presenting all sides of the story, from the fraught scientific competition to be the first to bring these drugs to market, to the side effects rippling through global societies, it uncovers.
Skinny is in. Around the world, waistlines are shrinking as millions upon millions inject a once-weekly drug. Designed to control blood sugar for those with Type 2 diabetes, it was found to have remarkable weight-loss benefits. Soon, diabetics had difficulty getting their prescriptions filled because demand for the drug was so strong that manufacturing couldn’t keep up with demand.
The molecule known as semaglutide is being touted as a miracle drug. Sold under brand names like Ozempic or Wegovy, it has begun to reshape societies. While this success might appear to have come overnight, the search for a better treatment for blood sugar management actually started decades ago, with the pioneering efforts of biochemists on two sides of the Atlantic. This lesson dives deep into the story of the creation of these drugs, their promise and benefits. But it also tackles the less glamorous side of weight-loss miracles: the serious side effects and negative impacts of treating obesity in an increasingly overweight world. Whether you’re curious about the “jab” that everyone is talking about, or want to know more about a treatment that is already changing your life, this lesson is for you.
According to the World Health Organization, between 1976 and 2006 the proportion of obese adults in the US population rose exponentially, to around thirty percent and rising. This number counts only those whose Body Mass Index, or BMI, is above 30. It does not include adults who are just overweight, or whose BMI is between 25 and 30. In 2023 the Centers for Disease Control in the US estimated the number of overweight or obese adults nationally totalled more than 70 percent.
The trend reveals a lot about changes to society since the 1980s, the decade when the steepest climb in obesity rates began. But it also hides behind charts and numbers the real costs of increasing waistlines on individuals and communities. For instance, many obese individuals dread going to the doctor. Every health complaint, pain, or symptom they bring to their appointment is met with the same response: just lose weight. Obesity has been seen as a failure of willpower and self-control for decades, and the cause has always been assumed to be a flaw in character, not genetics or biochemistry. The result?
Increasing numbers of overweight or obese people avoided doctors, who peddled the same tired advice decade after decade: eat less, exercise more, you’ll lose weight. Patients who tried found themselves on a diet roller coaster that often saw them gaining more in the end. Others turned to surgeries, radical programs or intensive interventions that had serious consequences for their health. Meanwhile, the public belief that excess weight comes only from gluttony means patients who fail to lose weight face a life full of judgement from even the most well-meaning people in their lives. Like a cloak of shame, the excess weight is more than just a physical burden weakening joints and straining organ systems. It is the weight of harsh judgement.
No wonder so many carrying extra weight turn to larger potions or sweet treats for comfort, perpetuating an escalating, vicious cycle. And adults are not the only ones carrying the load. Children’s weight has seen a similar rise in recent decades. Rates of overweight and obese children had tripled, to around thirty percent, when First Lady Michelle Obama kicked off the Let’s Move initiative in 2010.
The goal was to cure the obesity epidemic in a generation. But even the Obamas understood there was no quick fix, and the program didn’t slow the growing crisis. Likely because there was an entire commercial food system keeping the weight gain rolling.
Individuals bear the burden of excess weight and obesity, along with the Type 2 diabetes, high blood pressure or heart disease that often accompany it. But the causes of obesity are far more collective. Social and cultural factors, governmental legislation, corporations and lobbyists all conspire to create the perfect conditions to produce obesity on a global scale. Starting in the 1980s, there was an intentional effort on the part of large brands like Kelloggs and Kraft to embrace the trend of abundance in their marketing efforts.
With the rise of households in which both parents worked, and the widespread adoption of the microwave oven, industrial food producers recognized the growing need for convenience foods. Households had less and less time to cook meals from scratch. Food companies soon realized that they could make far more money selling ultra-high processed foods, like microwave meals and packaged snacks. By just 1994 the US Department of Agriculture’s estimate of food advertising spending reached 36 billion dollars a year. This money was spent entirely on the effort to get Americans to eat more. It played up any nutritional benefits, like added vitamins and minerals, while never mentioning the added sugar, salt, stabilizers, preservatives, emulsifiers, and coloring.
Meanwhile, soft drink companies, like Coca-Cola and Pepsi, were spending billions on lobbying to stay available in schools. Food companies redesigned their highly processed breakfast cereal boxes with cartoon characters in bright colors to appeal directly to kids. These characters appeared relentlessly in ads aired during children’s television programs. Yet one serving of Smacks, a sweetened puffed-wheat cereal, contains as much sugar as a Snickers bar. Fast food companies also responded to this demand for quick meal options and abundance by increasing the portions of food items. By 2002, for instance, the “large” size of McDonald’s french fries was equivalent to one that was considered “supersized” in 1998.
Over the same decades, other aspects of life were also changing. More people working meant that most adults had little time for pursuing sports, recreation, or hobbies. Program cuts and less physical education in schools made sedentary lifestyles seem normal. Economic shifts left entire neighborhoods as food deserts, or those in which only fast or processed food options were available. So while individuals are judged for the eating choices that led to weight gain, there is a global system driving obesity across all levels of society. Fortunately, efforts were already underway in an obscure area of science that held the promise of a solution.
When Svetlana Mojsov stepped off a plane at JFK Airport in 1972, she was coming to New York to pursue her PhD in biochemistry fresh from the University of Belgrade. She’d learned about Rockefeller University, a private postgraduate institution for biochemical research in New York, from a former professor who’d taken a sabbatical at Columbia University. Young and full of optimism for her future, she was eager to make her mark in research. Raised in the former Yugoslavia, she was astonished at the portion sizes in America.
Having rarely seen meat growing up, the average T-bone steak served in New York restaurants was more meat than she’d seen in her lifetime. She couldn’t remember seeing an obese person growing up, but she saw many on her campus at Rockefeller University participating as research subjects. That’s because to a growing number of researchers, the idea that obesity was only about willpower was simplistic at best. More were coming to see obesity as a disease that could be treated. Laboratory research with mice had proven that hormones like leptin helped some animals feel full with less food, keeping them slim. If appetite was controlled by hormones, then hormones could hold the key for weight loss.
As far back as 1976, researchers like Jens Juul Holst at the University of Copenhagen, were attending international biomedical conferences discussing the possibility of unknown gut hormones controlling appetite and overall health. But there was still considerable mystery around what caused some to gain while others stayed slim on similar diets. They were also faced with the exponential rise in Type 2 diabetes cases that shadowed the rise in obesity. Insulin, the earliest treatment, was harvested from pigs. But the number of diabetes patients had doubled between the 1950s and the 1970s alone. If the diagnoses kept increasing at this rate, pig supply couldn’t keep up with demand.
At Rockefeller University, Mojsov focused on studying glucagon, a hormone discovered back in the 1920s that was shown to affect blood sugar. She hypothesized that if harnessed correctly, it could be used to help treat diabetes. But to do this, she would have to synthesize a chemical version in the laboratory. With necessity as the mother of invention, she set about to do just that, and pioneered a method for synthesizing large quantities of protein molecules, known as peptides, in the process.
This breakthrough both launched Mojsov’s career, and placed her at the forefront of a race on both sides of the Atlantic to synthesize a hormone-based drug that could help control blood sugar. In the decades following Mojsov’s breakthrough in peptide synthesis, research into this area exploded. Mojsov’s synthesized peptides drove research at her new position as an associate in biochemistry at Massachusetts General Hospital.
She was initially hired by Michael Rosenblatt, the head of the endocrinology unit, to synthesize proteins for other researchers. But by the Fall of 1983, she was director of the Peptide Synthesis faculty at Mass General, and appointed an associate of the Howard Hughes Medical Institute. This gave her funding and time to pursue her own research. There she continued her work on glucagon and spent years doing animal studies attempting to establish its forms and effects in animals.
Her former mentor at Rockefeller, Bruce Merrifield, with whom she shared her preliminary results, strongly urged her to document her experiments in laboratory notebooks. Advice that turned out to be essential in years to come. Especially when fellow scientist at Mass General, Joel Habener, heard about her research. Soon a member of Habener’s team, Canadian biochemist Daniel Drucker, approached Mojsov about collaboration. Habener’s lab had identified a glucagon-like molecule in the bellies of fish, dubbed GLP-1, for glucagon-like peptide. Though reluctant to share her process, Mojsov was aware that collaboration could speed up their progress.
In September of 1986, Mojsov and Habener published their first joint paper, identifying GLP-1 in the gut and tracing its active forms. This paper was published in the very same month that Jens Juul Holst in Copenhagen was presenting the same experimental findings at a conference in Italy. Two teams were on the trail of GLP-1 as a potential diabetes treatment, and reaching the same breakthroughs simultaneously. Just a year later, however, Mojsov had a second breakthrough when she used a method pioneered by Gordon Weir, who had discovered a method to monitor insulin in rat pancreases in real time using GLP-1 synthesized by Mojsov. Using Weir’s method, she injected GLP-1 into rat pancreases and was able to confirm its effects. The results were published in 1987 with Mojsov and first author, Weir and Habener as second and third.
Just fifteen years after arriving in New York, she had confirmed GLP-1’s role in releasing insulin. Like so many other women in science both before and after, Mojsov would go on to have to fight for her place in this groundbreaking discovery through protracted lawsuits about patent rights. Her careful documentation of the process meant she eventually received thirty percent of the outsized revenue her discovery garnered. But there was still a long way to go before her pioneering work could result in new treatments. That breakthrough would come from far away and the most unlikely of sources: the belly of a lizard.
Four years after the GLP-1 breakthrough by Mojsov and others in Massachusetts, biochemist John Eng at the Veterans Affairs Medical Center in the Bronx was pursuing similar research into gut hormones. Remembering a paper by a Belgian scientist who noted that the Gila Monster, a lizard living in harsh desert environments, had remarkably stable blood sugar despite eating only a few times a year. In 1990 Eng isolated a molecule in reptile venom that worked very much like GLP-1 but had more long-lasting effects. This was important because with GLP-1’s role confirmed in blood sugar regulation, drug companies faced another problem.
The human body has enzymes that chop up the peptide when it is encountered outside the pancreas. This means that ingesting or injecting GLP-1 is useless. Biochemical researchers around the world were trying to be the first to create a viable GLP-1 drug that would evade the body's defense mechanisms long enough to provide lasting stability for sugar levels Eng’s discovery spurred researchers back in Copenhagen at the headquarters of Novo Nordisk, the European pharmaceutical giant. There, chemist Lotte Bjerre Knudsen was attempting to directly harness Mojsov’s breakthroughs in GLP-1. She had expertise in enzymes, and eventually collaborated with her boss, biochemist Mads Krogsgaard Thomsen, for the research. But they were beaten to the launch by a small San Diego pharmaceutical company in 2005.
John Eng had licensed the Gila Monster compound, which was launched under the name Byetta. Thomsen and Knudsen were devastated, but Byetta had a major drawback: it had to be injected twice daily. They headed back into the laboratory to experiment with similar molecules that needed fewer doses. In 1997, they succeeded in formulating a long-lasting glucagon-like peptide, liraglutide. First tested on rats, liraglutide had remarkable benefits for stabilizing blood sugar. Early studies also showed it caused appetite suppression, meaning the drug had weight loss benefits.
But in 2003 it was shown to cause tumors in the thyroids of test rats. The drug was eventually released when it was proven the tumor mechanism was unique to mice and rats, but this took time, and liraglutide needed to be injected daily. Thomsen, however, had been secretly experimenting with a similar peptide, semaglutide, as well. And that molecule was already exceeding all earlier GLP-1 versions for both stability and effectiveness. It required injection only once a week and showed no tumor risk. It was eventually released as Ozempic and hit the US market in 2018, marking the culmination of almost fifty years of research.
An ad campaign mounted in July of that year touted it as “magic” It certainly appeared that way. Users taking Ozempic to control blood sugar lost 17 to 18 percent of their body weight compared to 2 to 3 percent for dieters. The results also lasted as long as the patient stayed on the drug. Not only could it control blood sugar, semaglutide could also attack the underlying cause of diabetes and fight obesity.
Soon after the launch by Novo Nordisk, other drug companies followed suit with their own versions of GLP-1 agents, like Tirzepatide and Dulaglutide. As manufacturers struggled to keep up with demand, social media began to explode with weight loss stories from those who had struggled their entire lives. Semaglutide drugs began bringing in billions for drug companies, too. The estimated market share for drugs like Ozempic rose to almost 25 billion between 2018 and 2025, with 2026 projected to raise that number to over 28 billion.
With millions of individuals now on these drugs, it was only a matter of time before the news of side effects began appearing Some side effects were quite positive. For instance, Clothilde first heard of Ozempic when she’d seen a new doctor in early 2019. She’d long been discouraged by her excess weight, despite staying active and being careful about her diet. She’d borne the shame of doctors scolding her for any kilo gained, a common practice by doctors in France. This time, however, she left the doctor’s office with a new prescription for a once-a-week injection. Almost from the first dose, she noticed something remarkable: an inner silence.
She’d not realized how much she obsessed all day every day with what she would eat, and when. This voice had buzzed in her head since she was a little girl. Not only did she lose weight, food was no longer at the center of her life. Other patients weren’t so lucky. Some couldn’t get over the initial nausea. Semaglutide essentially slows down digestion and stomach emptying.
Nausea is common and in some cases severe. Others, like Jorge, who’d begun semaglutide after his physician diagnosed him with both obesity and pre-diabietes, had more severe side effects. For a small but significant portion of semaglutide patients, the gut-slowing effect of the medication is powerful. Even at the lowest doses, patients like Jorge had severe nausea from day one, but shedding weight made him continue. Soon, the daily nausea and vomiting was accompanied by terrible gas and stomach cramps. He was found to have developed gastric paresis, or a paralysis in his gut, which was likely permanent.
Similar patients had full or partial colostomies, meaning parts of their gut needed to be removed. For a smaller group of semaglutide users, the risks are even more severe. For people with body dysmorphia, both the hype and the flood of semaglutide drugs into the market has been dangerous. Those chasing more and more distorted views of thinness have driven the black market for semaglutide drugs into a frenzy – many braving the risk of counterfeits to achieve a skinny ideal.
However they risk malnutrition, major organ failure, and ultimately death in this reckless pursuit of thinness. One thing is certain. Just five years after launch, semaglutide and its derivatives are reshaping society. What remains to be seen, is at what cost.
The main takeaway of this lesson to Off the Scales by Aimee Donnellan is that… Though semaglutide drugs like Ozempic or Wegovy might seem to have appeared overnight, they were the result of long-term biochemical research in laboratories around the world. Building on major discoveries on the role of complex protein molecules, known as hormones, scientists in the US and Denmark raced to isolate and synthesize the glucagon-like proteins that help control blood sugar in animals to treat humans. Almost 50 years after glucagon was first synthesized in a laboratory, scientists at Novo Nordisk launched a glucagon-like molecule, semaglutide under the brand name Ozempic. Within months, demand for the drug, which not only controlled blood sugar but served as an appetite suppressant, started to outstrip supply.
In the five years since release, this class of drugs has begun to reshape not only individual waistlines, but the culture at large.
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