After learning that Gila monster lizard venom contains hormones that can regulate blood sugar, Daniel Drucker began to wonder why. And can poison help cure diabetes?
Drucker is an endocrinologist at the University of Toronto who has dedicated his career to understanding the universe of hormones in the body that do everything from regulating appetite to aiding digestion. His curiosity about Gila’s monster led him to call the Utah Zoo. In 1995, Drucker moved a lizard from Utah to his lab and began experimenting with deadly venom.
Ten years later, a synthetic version of the poison hormone became the first drug of its kind to be approved for the treatment of type 2 diabetes. Known as the GLP-1 (glucagon-like peptide-1) receptor agonist, the drug launched a cascade of additional poison-inspired discoveries.
After doctors found that mice and people who found a cure for diabetes were losing weight, they began to consider its use in the science of obesity. In June 2021, another effective treatment for this obesity was approved by the Food and Drug Administration. Named Wegovy, marketed as semaglutide, it also derives its structure from lizard venom.
If this story of origin seems strange, consider the history of obesity treatment. Over the years, people have resorted to extreme, incredible interventions to lose weight, from jawbones, laxatives, vagotomy to band surgeries, to fen-fen, a “miracle” diet drug that was eventually recalled.
The new treatment, which is injected once a week from Novo Nordisk, a Danish pharmaceutical company that has hired consultants from many leading obesity scientists, is ready to help many obese people with health problems, say doctors and researchers. It may even shed light on some of the mysteries of how appetite works in the first place.
“It’s phenomenal,” said Michael Creshes, a diabetes researcher at the National Institutes of Health. Semaglutide is a big step forward. “We finally have something reliable that can have a lasting effect over time,” said Ivan de Araujo, a neuroscientist who studies the brain-intestinal interactions at Mount Icana School of Medicine in Mount Sinai. No scientist is associated with Novo Nordisk.
Doctors treating Tors-obsessed patients told Vox that they would like to have a treatment like semaglutide years ago, with patients describing the drug as life-changing.
Although many people with obesity may not be able to look for semaglutide, doctors may not prescribe it not only because of the dangerous history of weight loss drugs, but also because of the stubborn bias of the disease, which now affects almost half. Americans Ob obsession is still widely regarded as a matter of personal responsibility, despite scientific evidence to the contrary. And history has shown that the most effective medical interventions, such as bariatric surgery, the current gold standard in the treatment of obesity, often remain unused in favor of diets and physical exercises that do not work for many.
There is also a practical challenge. Health insurers do not usually prescribe anti-obesity drugs, says Scott Kahan, an obesity physician and professor at John von Hopkins Bloomberg School of Public Health, Washington University School of Medicine, Washington University School of Medicine. “Medicare explicitly excludes over-the-counter medications,” said Kahan, who is consulting with Novo Nordisk. “And most insurers are lagging behind what Medicare does.”
The new drug, of course, will not be all the means to fight obesity, adds Crasses. “You do not take 0 280, you make և 130,” he says, although the cuts that are enough to improve health are typical. Drucker, who began consulting with Novo Nordisk and other pharmaceutical companies after discovering the reptiles, agrees that this is the starting point for obesity. “It will only scratch the problem area of the population, which should be healthier.”
But semaglutide is the most powerful over-the-counter obesity drug, he adds. “Drugs that will create 15% weight loss. “We have never had it before in medical obesity therapy.” With additional, potentially more effective GLP-1 receptor agonists coming online in the future, we are at the beginning of a promising new chapter in obesity therapy. A look at the fascinating science of how medicine works can greatly change the way Americans think about the disease.
“We have to thank the lizard for that,” Drucker said.
What does semagglutin reveal about weight problems?
To understand how semaglutide is eaten by some people, it is helpful to understand what hormones do. These are the messengers that travel the body. Produced in one area, they are transported to another space through receptors to transmit messages to distant organs և cells through molecules that bind to specific hormones.
The gut produces dozens of hormones, և Many of them are directed to brain receptors that either suppress or stimulate appetite. GLP-1 is one of the intestinal hormones. It is released into the gut in response to food: stimulates the pancreas to produce more insulin after a meal, which lowers blood sugar. (GLP-1 is also made in the brainstem, where it can change appetite.)
“It sends a signal to our brain saying, ‘You know, we’re enough to eat,'” Drucker said.
Enter semaglutide, a class of drugs called GLP-1 receptor agonists that mimic GLP-1 to help the body lower glucose (in people with diabetes), հետազոտ as researchers suspect, suppress appetite (in obese people who can to have diabetes!
The exact effect of the drug on obesity is not yet known, in part because scientists do not understand the proper use of appetite. But researchers generally agree that the drug uses the brain’s GLP-1 receptors to inhibit food intake. When researchers removed GLP-1 receptors from the brains of mice, the drug lost its appetite suppressant effects, Crashes said.
Ob obsession is “primarily a matter of our brain biology, the way it processes information about our environment,” says Randy Seale, a University of Michigan-based obesity researcher who also advises Novo Nordisk. with:
The idea with semaglutide is that “we change the chemistry of your brain so that your brain believes that you need to lose weight,” added Cili.
A brain-based pharmacological approach is likely to be more successful than diet and exercise alone, says Cill, because “the strongest basis for someone’s weight is their brain function” rather than a lack of willpower.
Not so “game changer”
Some people with a higher body mass index are perfectly healthy and do not require any treatment. Semaglutide has been reported by the FDA only for patients who are classified as clinically obese, with a body mass index of 30 30 or more, or those who are overweight և have at least one weight problem.
For many people who use it, according to the FDA, it has proven to be safe and effective. In clinical trials of weight loss, semaglutide helped people lose an average of about 15 percent of their body weight, significantly more than currently available obesity drugs, and more than enough to improve health outcomes.
The most common side effects of the drug – nausea, diarrhea, constipation – vomiting, mostly brief. De Araujo believes that adverse reactions can be caused by how the drug differs from the natural peptide hormone. The hormone acts mainly locally և is rapidly degraded, while the drug acts mainly on the brain է is intended to remain in the body. “This is probably where nausea and vomiting come from,” says De Araujo.
Patients who have tried semaglutide have told Vox that it helps them control their weight, their dietary interactions, their side effects are manageable, and they resolve quickly.
Ohio 911 cameraman Jim my Egeman said that before taking semaglutide, “I could sit down and eat a big pizza, but now it’s a maximum of one or two pieces.” She started taking diabetes medicine in December 2019 after a heart attack and lost 35 kilograms, bringing her weight to 220.
Paula Morris-Kaufman, from the city of Cheshire, UK, has used the drug to gain weight as a result of cancer treatment. It helps her maintain a normal weight, she says, ելու curbing the habit of forced eating. “If you give me a plate of food, I eat a small portion of it; I feel really full quickly.”
It is possible that some of the benefits of treatment come in part from lifestyle changes that have been encouraged in clinical trials. In many cases, patients with semaglutide also switched to a healthier diet when they started medication and added exercise to their regimen. But participants in a drug study lost significantly more weight than those in the same condition who received a placebo.
The need for additional interventions, such as diet and exercise, is one of the reasons why Kahan stops calling this drug a game changer. “It’s a gradual improvement over existing drugs,” he says, “still out of reach for those who can use it.” “The description of the ‘game changer’ is inappropriate, as many of these drugs are not available.”
Change of thinking
The study showed that in 2019, only 1% of eligible patients were using FDA-approved anti-obesity drugs. The same is true of bariatric surgery, which is currently the most effective treatment for obesity, which can lead to remission of type 2 diabetes.
“If someone enters your office with heart disease, you’s not trying to cure it as a doctor, it’s illegal,” says Cili. “If someone comes with a BMI over 30, you do not treat it, it is Tuesday.” He believes that some of the fluctuations in the treatment of obese patients come from the history of dangerous weight loss drugs.
The priest says that the cunning biases associated with obesity also made it difficult for patients to enter. “Insurance harassment tends to be classified as a cosmetic problem in health insurance policies,” he says. “In order to get Coverage coverage, employers must clearly decide to buy a rider և sign a contract to add weight management services և products to their insurance plans.” He would like to see obesity treatments covered by insurers, such as diabetes and hypertension.
That would require a change of mindset, says Drucker. “We will never blame other people for developing high blood pressure or cardiovascular disease or cancer,” he said. It is well known that these conditions are caused by complex biological determinants, including genes as well as environmental factors. “Ob protection is no different.”
When Drucker began endocrinology in the 1980s, he did not have many tools to help patients. With the addition of semaglutide, there are many surgical options և drugs against obesity: diabetes. Now the challenge is for those who will benefit to enter.
“I would be happy if no one needed GLP-1 for obesity,” says Drucker. It would be possible in the field of food that did not drive people to overeating, poor diet, which leads to these chronic conditions. But for now, “we have new options that are safe, seem to reduce complications, are very effective. “We should not just throw up our hands and say we can do nothing.”