In the last week of December, while much of the US was still in furlough mode, Novo Nordisk's plant in North Carolina was running at full capacity.
On December 22, the U.S. Food and Drug Administration (FDA) approved the oral version of Wegovy, making it the first pill of the popular GLP-1 drug to get the green light for weight loss. People who want to lose weight and are prescribed Wegovy now have the option of taking the pill daily rather than having to inject themselves with the drug once a week. With either option, they will lose about the same amount of weight: 16% to 17% of their original body weight.
The plant, located near Raleigh, operates around the clock and produces the tablets in four different strengths. The bottles are intended for retail stores and online pharmacies and will be available starting January 5th. “Obesity has become a consumer-driven disease,” Novo Nordisk CEO Mike Dustdar told TIME. “We accept it.”
All of the company's drug supply will be made in North Carolina from start to finish. A few days before the launch of Wegovy tablets, TIME magazine visited the plant to see how the first Wegovy tablets were produced, bottled and packaged for patients.
It all starts with yeast
The veg pill starts with a fungus: specifically, the same yeast from which bread is baked, called Saccharomyces cerevisiae. But instead of fermenting sugar or grains to make bread rise, yeast cells are genetically modified at Novo Nordisk's Clayton, North Carolina, facility to produce protein, which is fermented in several four-story tanks and then undergoes several purification steps over the course of a month to produce semaglutide, a compound that mimics the human hormone that regulates appetite by affecting the brain's reward center. This can help people feel full and reduce hunger.
Collecting the main ingredient
After the fermentation and purification process, semaglutide forms a beige paste with the consistency of pancake batter. In one of the few manual steps in largely automated production, technicians scrape the paste out of large funnels and freeze it at -20°C, where it will keep for up to five years. But given Wegovy's popularity and expected demand for the tablets, the company currently has a month's supply of semaglutide in its freezers.
Taking pills
At the final stage of the process, the paste is thawed and purified to liquid at high temperature. This heated liquid is then spray dried into a fine white powder, similar to how snow blowers turn hot water into snow. This powder is collected into large bags from a funnel running through three floors and then compressed into Wegovy tablets.
Long way to the pill
Although this semaglutide tablet is the first for treating obesity, it is not the first to be launched by Novo Nordisk. The company's scientists first became interested in semaglutide as a treatment for diabetes because it can also help control blood glucose levels, and its first semaglutide therapy, Ozempic, was approved in 2017 for the treatment of diabetes. Patients injected themselves once a week to control their blood sugar levels, but to make the drug easier to take, the company also developed a tablet form called Rybelsus, which the FDA approved in 2019. Turning Ozempic into an oral tablet required finding a way to protect the drug from the harsh environment of the stomach long enough for it to be absorbed by the body. “But using many of these strategies would result in too much permeability—so things that shouldn't be absorbed, like bacteria or other things, get absorbed,” says Andrea Traina, senior medical director for obesity and liver health at Novo Nordisk. Scientists eventually found a way to create a chemical buffer that protects the drug while it releases enough semaglutide to work. However, because the tablet must pass through the stomach and digestive tract, it is generally not as effective as the administered Ozempic.
When diabetic patients noticed they were losing weight while taking semaglutide, Novo Nordisk and other companies began studying the compound for its potential effects on obesity. Research confirmed what these patients were experiencing, and in 2021 the FDA approved Novo Nordisk's Wegovy for the treatment of obesity. But people still had to inject themselves with the medicine to get its effect. Developing the Wegovy tablet was the next challenge, and the same obstacles the company faced in developing Rybelsus remained. But this time, researchers have developed a proprietary fatty acid derivative to better navigate the complex environment of the stomach. “After you swallow the tablet, it comes into contact with the stomach lining and begins to dissolve and create a foamy microenvironment around the tablet,” Traina says. “Imagine an Alka-Seltzer tablet dissolving in water.” The reaction temporarily prevents stomach enzymes from breaking down the drug in that area, giving semaglutide enough time to be absorbed. “The whole process takes about half an hour,” she says, after which “the microenvironment of the stomach returns to normal.” To maximize the pill's ability to be absorbed, people taking it should swallow it first thing in the morning on an empty stomach with up to half a glass of water, without food, drinks or other medications for at least 30 minutes, the company advises, to ensure nothing interferes with the pill's action.
Fierce competition
The Wegovy pill isn't the only GLP-1 weight loss pill on the horizon. Eli Lilly, which makes the injectable GLP-1 diabetes treatment Mounjaro and Zepbound for weight loss (using the active ingredient tirzepatide), developed a pill called orforglypron. In December the company published positive data demonstrating that its pill can help people maintain weight loss after using injectable forms of GLP-1 drugs for more than a year, and has submitted a request to the FDA for approval. Agency provided orforglipron with a priority voucher in November, meaning the FDA will conduct a fast-track review so the pills can hit the market much faster than a conventional drug.
Novo Nordisk and Eli Lilly have been competing in GLP-1 competitions for many years. Some research found that Lilly's Zepbound resulted in greater weight loss—up to 21% of body weight—compared to 15% with Wegovy. “The difference has a lot to do with the doses,” says Dustdar; The highest dose of tirzepatide is higher than that of semaglutide in Vegovoy. For this reason, Novo Nordisk is developing a higher dose of Vegovi in an injectable form that provides comparable weight loss of approximately 20%. “We will bring Wegovy-Plus to market. [in 2026] so this will close the gap with our competitor,” he says.
He also considers semaglutide the company's “secret sauce,” which appears to provide a number of health benefits. It is the only GLP-1 drug that the FDA allows on its label to make claims for heart disease and some liver diseases. Although recent studies have shown that The compound did not slow down Alzheimer's diseaseAs many had hoped, the drug's ability to reduce inflammation could lead to additional health benefits in other metabolic diseases.
Dustdar, who was named head of Novo Nordisk last summer when the company began losing market share in GLP-1 to Eli Lilly, sees the Wegovy pill as a coup for the company and a return to a focus on diabetes and obesity. “This is a large disease area. We're talking about two billion people, and eventually someone has to produce all the doses for them. We're sitting in the right place now. [to do that]and still only affects a fraction of the people in need.”
Tablet options
In the coming weeks, Wegovy tablets will be available in four strengths: a starting dose of 1.5 mg, as well as 4 mg, 9 mg and 25 mg. As with the Wegovy injection, most patients start with the lowest dose and gradually increase the dosage over several months until they reach the maximum dose at which they will continue to maintain their new weight.
Like the company and the White House announced In November, the starting dose will cost $149 for a month's supply for people paying out of pocket and on federal insurance plans. The next highest dose will be $149 until April 2026, after which it will increase to $199 per month. The two highest doses will cost $299 for a month's supply of pills. People with insurance plans that cover the pills can pay as little as $24 for a 30-day supply.
Dustdar says the White House announcement follows months of discussions to reach a mutually acceptable pricing plan for the drug. “For us to do any kind of deal, it has to be a win-win situation rather than a zero-sum game,” he says. “We needed to explain that the cost of operations in the US is very different from the cost of operations in Europe.”
“On the other hand, we also understand that at higher prices we won't have access to larger volumes,” he says, “and with hundreds of millions of people around the world potentially benefiting from a weight-loss drug, Dustdar hopes Wegovy tablets will be more convenient and affordable for them.
