After learning that the venom of a Gila monster lizard contained hormones that can regulate blood sugar, Daniel Drucker started wondering why. And could the venom somehow help treat diabetes?<\/p>\n
Drucker is a scientist and endocrinologist at the University of Toronto who has dedicated his career to understanding the universe of hormones in the body, which do everything from regulating appetite to helping with digestion. His curiosity about the Gila monster led to a call with a zoo in Utah. In 1995, Drucker had a lizard shipped from Utah to his lab and began experiments on the deadly venom. <\/p>\n
Ten years later, a synthetic version of a hormone in the venom became the first medicine of its kind approved to treat type 2 diabetes. Known as a GLP-1 (for glucagon-like peptide-1) receptor agonist, the medicine set off a cascade of additional venom-inspired discoveries.<\/p>\n
After doctors noticed mice and humans on the drug for diabetes appeared to lose weight, they began to consider its use in obesity science. In June 2021, another effective treatment, this one for obesity, got Food and Drug Administration approval. Called semaglutide and marketed as Wegovy, it also takes its structure from the lizard\u2019s venom. <\/p>\n
If this origin story sounds outlandish, consider the history of obesity treatments. Over the years, people have turned to extreme and unlikely interventions to try to lose weight, from jaw wiring, laxatives, and vagotomies to lap band operations and fen-phen, a \u201cmiracle\u201d diet drug that was ultimately recalled. <\/p>\n
The new treatment \u2014 a once-weekly injectable from Novo Nordisk, a Danish pharmaceutical company that has hired many leading diabetes and obesity scientists as consultants \u2014 is poised to safely help many people with health-threatening obesity, physicians and researchers say. It may even illuminate some of the mysteries around how appetite works in the first place. <\/p>\n
\u201cIt\u2019s phenomenal,\u201d says Michael Krashes, a diabetes and obesity investigator at the National Institutes of Health. Semaglutide is \u201ca big step forward \u2014 we finally have something that\u2019s reliable and able to produce sustained effects over time,\u201d adds Ivan de Araujo, a neuroscientist who studies brain-gut interactions at Mount Sinai\u2019s Icahn School of Medicine. Neither scientist is affiliated with Novo Nordisk. <\/p>\n
Doctors who treat obesity patients told Vox they wished they had a treatment option like semaglutide years ago, and patients described the drug as life-altering. <\/p>\n
Yet many people with obesity may not seek out semaglutide, and doctors may not prescribe it to them \u2014 not only because of the dangerous history of weight loss medications, but also because of a persistent bias and stigma around a disease that now afflicts nearly half of Americans. Obesity is still widely viewed as a personal responsibility problem, despite scientific evidence to the contrary. And history has shown that the most effective medical interventions, such as bariatric surgery \u2014 currently the gold standard for treating obesity \u2014 often go unused in favor of dieting and exercise, which for many don\u2019t work. <\/p>\n
There\u2019s also a practical challenge: Health insurers don\u2019t typically cover obesity medications, says Scott Kahan, an obesity doctor and professor at Johns Hopkins Bloomberg School of Public Health and the George Washington University School of Medicine. \u201cMedicare explicitly excludes weight medications,\u201d Kahan, who consults with Novo Nordisk, says. \u201cAnd most insurers follow what Medicare does.\u201d <\/p>\n
The new drug certainly won\u2019t be a cure-all for obesity, Krashes adds. \u201cYou are not taking a 280-pound person and making them 130,\u201d he points out, though reductions that are enough to improve health outcomes are typical. Drucker, who began consulting with Novo Nordisk and other drug companies after his reptilian discovery, agrees that it\u2019s a starting point for obesity: \u201cIt will only scratch the surface of the problem in the population that needs to be healthier.\u201d <\/p>\n
But semaglutide is the most powerful obesity drug ever approved, he adds. \u201cDrugs that will produce 15 percent body weight loss \u2014 we did not have that before in the medical therapy of obesity.\u201d With additional, potentially more effective GLP-1 receptor agonists coming online in the future, we\u2019re at the beginning of a promising new chapter of obesity therapeutics. A look at the fascinating science of how the medication works could also go a long way to changing how Americans think about this disease. <\/p>\n
\u201cWe have to thank the lizard for that,\u201d Drucker says.<\/p>\n
What semaglutide reveals about weight problems <\/p>\n
To understand how semaglutide causes some people to eat less, it\u2019s helpful to understand what hormones do. They\u2019re the body\u2019s traveling messengers: Manufactured in one area, they move to another to deliver messages through receptors \u2014 molecules that bind to specific hormones \u2014 in distant organs and cells. <\/p>\n
The gut makes dozens of hormones, and many of them travel to the brain receptors that either curb appetite or stimulate it, Drucker explains. GLP-1 is one such gut hormone. It\u2019s unleashed in the gut in response to food and stimulates the pancreas to make more insulin after a meal, which lowers blood sugar. (GLP-1 is also made in the brain stem, where it may modify appetite.) <\/p>\n
\u201cIt sends a signal to our brain that says, \u2018You know, we\u2019ve had enough to eat,\u2019\u201d says Drucker.<\/p>\n
Enter semaglutide, one of a class of medicines \u2014 the GLP-1-receptor agonists \u2014 that imitate GLP-1, helping the body lower glucose (in the case of people with diabetes) and, researchers suspect, curb appetite (in the case of people living with obesity who may also have diabetes).<\/p>\n
The precise way the drug works on obesity is still unknown, in part because scientists don\u2019t understand exactly how appetite works. But researchers generally agree that the drug harnesses the brain\u2019s GLP-1 receptors to curb food intake. When researchers delete the GLP-1 receptors from the brains of mice, the drug loses its appetite-suppressing effects, says Krashes.<\/p>\n
Obesity is \u201cprimarily an issue of our brain biology, and the way it\u2019s processing info about the environment we live in,\u201d says Randy Seeley, a University of Michigan researcher focused on obesity treatments, who also consults with Novo Nordisk. <\/p>\n
With semaglutide, the idea is that \u201cwe\u2019re changing your brain chemistry for your brain to believe you should be at a lower weight,\u201d Seeley added. <\/p>\n
This brain-based pharmacological approach is likely to be more successful than diet and exercise alone, Seeley says, because \u201cthe most important underlying part of somebody\u2019s weight has to do with how their brain operates,\u201d not a lack of willpower.<\/p>\n
Not quite a \u201cgame changer\u201d <\/p>\n
Some people with a higher body mass index are perfectly healthy and don\u2019t require any treatment. Semaglutide was only indicated by the FDA for patients who classify as clinically obese \u2014 with a body mass index of 30 or greater \u2014 or those who are overweight and have at least one weight-related health problem. <\/p>\n
For the many people who have used it, it has proved safe and effective, according to the FDA. In weight loss clinical trials, semaglutide helped people lose about 15 percent of their body weight on average \u2014 significantly more than the currently available obesity drugs and more than enough to improve health outcomes. <\/p>\n
The drug\u2019s most common side effects \u2014 nausea, diarrhea, constipation, and vomiting \u2014 were mostly short-lived. De Araujo is finding that adverse reactions might be caused by how the drug differs from the naturally occurring peptide hormone: The hormone acts mostly locally and degrades quickly, while the medicine works mainly on the brain and is designed to stick around in the body. \u201cThat\u2019s where the nausea, vomiting probably derive from,\u201d De Araujo argues. <\/p>\n
Patients who have tried semaglutide told Vox that it helped them manage their weight and relationship to food, and that their side effects were manageable and quickly resolved. <\/p>\n
Jim Eggeman, a 911 operator in Ohio, said that before taking semaglutide, \u201cI could sit down and eat a large pizza, and now it\u2019s one to two pieces at the most.\u201d He started on the drug for diabetes after a heart attack in December 2019 and lost 35 pounds, bringing his weight to 220. <\/p>\n
Paula Morris-Kaufman, of Cheshire, UK, used the drug to address weight gain following cancer treatments. It helped her bring her weight back to a normal range, she says, and curb her habit of compulsive eating. \u201cIf you give me a plate of food, I just eat a small portion of it \u2014 and feel full really quickly.\u201d <\/p>\n
It\u2019s possible that some of the benefits of treatment come in part from lifestyle changes, which were encouraged by the clinical trials. In many cases, patients on semaglutide also switched to a healthier diet when they started on the drug and added exercise to their routines. But study participants taking the drug still lost significantly more weight than those under the same conditions who received a placebo. <\/p>\n
The need for additional interventions \u2014 like diet and exercise \u2014 is one reason why Kahan stops short of calling this drug a game changer. \u201cIt\u2019s an incremental improvement\u201d over existing drugs, he says, and it\u2019s still out of reach for many of the individuals who could benefit from it. \u201cThe \u2018game changer\u2019 description is not appropriate, because many people don\u2019t have access to these medicines.\u201d <\/p>\n
A mindset shift <\/p>\n
Only about 1 percent of eligible patients were using FDA-approved medications for obesity in 2019, a study showed. The same is true for bariatric surgery, currently the most effective intervention for obesity, which can also drive type 2 diabetes into remission.<\/p>\n
\u201cIf someone walks into your office with heart disease and you as a physician don\u2019t try to treat it, that\u2019s malpractice,\u201d Seeley says. \u201cIf somebody comes in with a BMI over 30 and you don\u2019t treat it, that\u2019s Tuesday.\u201d He thinks some of the hesitancy for treating patients with obesity medications comes from the history of dangerous weight loss drugs. <\/p>\n
Ingrained biases about obesity have also made it harder for patients to get access, Kahan says. \u201cObesity tends to be categorized as a cosmetic issue in health insurance policies,\u201d he says. \u201cIn order to get coverage, employers have to explicitly decide to buy a rider and sign a contract to add weight management services and products to their insurance plans.\u201d He\u2019d like to see obesity treatments covered by insurers in the same way diabetes and hypertension drugs are. <\/p>\n
That will require a shift in mindset, Drucker says. \u201cWe would never blame other individuals for developing high blood pressure or cardiovascular disease or cancer,\u201d he says. It\u2019s widely known that those conditions are driven by complex biological determinants, including genes, as well as environmental factors. \u201cObesity is no different.\u201d<\/p>\n
When Drucker started in endocrinology in the 1980s, he didn\u2019t have many tools to help patients. With the addition of semaglutide, there are multiple surgical options and drugs for obesity and diabetes. The challenge now is helping those who would benefit gain access.<\/p>\n
\u201cI would be delighted if no one needed GLP-1 for diabetes and obesity,\u201d Drucker says. That might be possible in a food landscape that didn\u2019t nudge people toward the overeating and poor diet that leads to these chronic conditions. But for now, \u201cwe have new options that are safe, appear to reduce complications, and are very effective. … We shouldn\u2019t just throw up our hands and say there\u2019s nothing we can do.\u201d<\/p>\n
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