Demand for drugs like Ozempic and Wegovy is soaring thanks to their weight-loss benefits, and now pharmaceutical companies are developing new pill versions that could make them even more popular.
Currently, these drugs must be injected into the thigh, waist, or upper arm once a week. Pills or tablets could be easier to take and more convenient for many patients. “Having another route of administration would be a huge benefit,” says Michael Weintraub, an endocrinologist and clinical assistant professor of medicine at NYU Langone Health. Many people have a fear of needles, and others may not want to be seen injecting a drug.
Last week, Novo Nordisk, which manufactures semaglutide under the brand names Ozempic and Wegovy, announced positive clinical trial results for a tablet form of the drug. In a trial of 667 adults who were overweight or obese, participants lost an average of 15.1 percent of their body weight over 17 months by taking the daily tablet, compared to people who lost 2.4 percent while taking a placebo pill. The results were comparable to a previous trial of weekly injections of Wegovy, in which people lost nearly 15 percent of their weight over the same period of time.
“The choice between a daily tablet or weekly injection for obesity has the potential to offer patients and health care providers the opportunity to choose what best suits individual treatment preferences,” said Martin Holst Lange, executive vice president for development at Novo Nordisk, in a company statement. The company plans to seek approval in the US and Europe for its tablet later this year.
Semaglutide was initially developed to treat type 2 diabetes. It mimics a hormone called GLP-1, which regulates insulin. But scientists found that it also led to weight loss in both lab animals and people. That’s because GLP-1 also signals to the brain when the stomach is full, so people who take these drugs have fewer cravings and a decreased appetite. Today, Ozempic is approved in the US and other countries to treat type 2 diabetes while Wegovy is specifically indicated for chronic weight management.
Novo Nordisk already makes a pill version of semaglutide, but it hasn’t shown the same weight-loss benefits as Ozempic and Wegovy. Called Rybelsus, it was approved in 2019 by the US Food and Drug Administration for type 2 diabetes. That pill is just 14 milligrams, while the tablet that the company is currently testing is 50 milligrams.
In the current study, researchers found that the new tablet was safe but that some patients had gastrointestinal side effects—the vast majority of which were mild to moderate and diminished over time, according to the company’s statement. The statement said the side effects were similar to ones patients experience on Ozempic and Wegovy. Those drugs can cause nausea, vomiting, bloating, constipation, and diarrhea. Often these occur in the beginning stages of taking the drug, when the dose is steadily increased, but drop off after several weeks.
“People can also get pretty dehydrated with these medications, because not only do you forget to eat but you also forget to drink,” says Kunal Shah, an assistant professor of endocrinology at Rutgers University who specializes in obesity treatment, referring to Ozempic and Wegovy.
Shah says a new pill with a higher dosage could potentially cause more frequent or severe instances of these side effects. “This is more than three times higher than what we normally give for oral semaglutide,” he says of the dosage for the experimental tablet. And because the current study compares the high-dose pill to a placebo, it’s not clear how the side effect profile of the new pill will stack up against the injectable version.
Novo Nordisk spokesperson Allison Scheider declined to give specifics on the risk of side effects, saying that these details would be presented later in June at a meeting of the American Diabetes Association.
Pfizer is also racing to make a weight-loss pill. Last week the company published positive results for its experimental medicine danuglipron, a different molecule that also imitates the GLP-1 hormone.
In a trial of 411 adults with type 2 diabetes that tested different doses of the pill, participants taking a high dose lost an average of around 10 pounds over four months, compared to those who received a placebo. The most common side effects were nausea, diarrhea, and vomiting. Most were mild in nature, but 57 participants didn’t continue in the study because of these side effects. As with other GLP-1 drugs, these side effects were more present early on in the treatment course and decreased over time, Pfizer spokesperson Jerica Pitts told WIRED via email. “Proper counseling in advance of the first dose can help patients keep on medication through these initial bumps,” Pitts wrote.
A pill version of these weight-loss drugs could come with strict instructions on how to take them. The existing semaglutide pill, Rybelsus, must be taken at least a half hour before any food, drink, or other oral medicines in the morning and can be taken only with a small amount of water. “Without abiding by those strict criteria, the absorption is going to be hindered,” Weintraub says.
Pfizer’s pill may have a leg up in this regard, Weintraub says, because its absorption isn’t affected by food, so patients could take it alongside a meal. However, Pfizer’s danuglipron must be taken twice a day, once in the morning and again in the evening. Pfizer has another diabetes pill in development, lotiglipron, that’s designed to be taken once a day. Both are in Phase 2 clinical trials, and Pitts said the company will make a decision by the end of the year about which to move forward into late-stage testing.
Semaglutide’s bioavailability—that is, how much of the drug reaches its destination—has been a challenge when formulating it into a pill, says Amy Rothberg, a physician and clinical professor at the University of Michigan Health who specializes in weight management and diabetes treatment. Injecting semaglutide is a more efficient way of getting it to the bloodstream, she says, which is why Ozempic and Wegovy injectors use just a tiny amount of the drug. But swallowing it in pill form means it has to pass through the digestive tract, where much of it is absorbed.
She thinks most of her patients would prefer a pill over the current injectable version. ”That being said, people forget their medications all the time. Patients would have to commit to taking something every day,” Rothberg says. After stopping Ozempic and Wegovy, appetite increases again, and many people who go off these drugs regain weight.
As for the cost of new weight-loss pills, Shah says they’re likely to be as expensive as the injectable versions—at least at first. “Anytime a new medication or a new version of a medication comes onto the market, the chances that insurance will cover it right away are pretty slim,” he says. While most insurers cover these drugs for diabetes, they’re not always covered for weight loss alone—and Ozempic and Wegovy respectively cost about $900 and $1,300 a month without insurance, according to Novo Nordisk’s list prices.
In an email, Novo Nordisk spokesperson Scheider said it’s too early to speculate about the price of a pill version. "Right now it is too early for us to provide comments on a price," Pitts also wrote about Pfizer’s pills in development.
