The next iteration of Ozempic and Wegovy — the much-discussed, hard-to-obtain injectable medications known for their ability to induce weight loss — may come in pill form.
Researchers presented data in two studies on Sunday at the American Diabetes Association Scientific Sessions conference, one of which showed that 50 milligrams of semaglutide — the active compound in Ozempic and Wegovy — taken orally each day is roughly as effective as weekly Wegovy shots in reducing weight in people who are overweight or obese. Wegovy injections contain 2.4 milligrams of semaglutide.
That trial, also published Sunday in The Lancet, tracked 667 people over 68 weeks. Eighty-five percent of those who took semaglutide lost at least 5 percent of their body weight over the course of the study, compared to just 26 percent of those who received the placebo. Those who took semaglutide lost, on average, around 15 percent of their body weight — roughly six times that of the placebo group.
A separate study, also presented Sunday and published in The Lancet, focused on oral semaglutide for people with Type 2 diabetes. Just over 1,600 participants were divided into three groups and given 14-milligram, 25-milligram or 50-milligram daily doses. Those who took the 25- and 50-milligram doses lost more weight, and had greater reductions in blood sugar, than those who took the lowest dose.
Novo Nordisk, the company that manufactures Wegovy and Ozempic, funded both trials.
“I suspect there are a lot of people that are not using these treatments because it requires an injection,” said Dr. Robert Gabbay, the chief scientific and medical officer of the American Diabetes Association. “If you could say, ‘Well, actually, it doesn’t,’ that’s big.”
The higher the dose of oral semaglutide, the more side effects seem to come with it. In the trial of people who were overweight or obese, 80 percent of those who took oral semaglutide reported gastrointestinal issues like vomiting, nausea, constipation or diarrhea. Nearly 13 percent said they experienced “altered skin sensation,” such as tingling. The majority of study participants were white and female, the authors noted, which means the results may not apply to the broader population of people with obesity.
The second trial, in people with diabetes, showed similar side effects: 80 percent of those who took the 50-milligram dose reported adverse effects, most commonly gastrointestinal issues, which occurred more frequently in people who took the higher doses than in those who took 14 milligrams. Thirteen percent of people who received the 50 milligram dose stopped taking the medication because of the side effects. Injectable semaglutide elicits similar side effects; in a previous study, 74.2 percent of participants who received 2.4 milligrams of injectable semaglutide each week (the amount that’s in Wegovy) experienced gastrointestinal disorders.
Another trial presented at the conference and published on Friday in the New England Journal of Medicine looked at a different oral compound, orforglipron, which belongs to the same class of medications as semaglutide. The study was funded by Eli Lilly. Pfizer has also tested its own pill in that drug class.
Oral semaglutide is not new: There’s already a tablet form of the compound on the market, sold under the name Rybelsus. The Food and Drug Administration has only approved that drug for adults with Type 2 diabetes, and the tablets come in comparably smaller daily doses, up to 14 milligrams. The tablets work in a similar way to semaglutide injections, which regulate insulin, lowering blood sugar and slowing the emptying of the stomach, making people feel fuller for longer periods of time, said Dr. Andrew Kraftson, a clinical associate professor at Michigan Medicine.
Rybelsus is less effective than Ozempic and Wegovy, Dr. Gabbay said.
It’s not clear when, or if, the higher-dose semaglutide pills might arrive on the market. An oral form may enable more people to take these medications, said Dr. Scott Hagan, an assistant professor of medicine at the University of Washington who has studied obesity, because there’s a lower barrier to entry to swallowing a pill, for some people, than injecting a drug. “It’s a welcome addition to treatment options for patients who may benefit from weight management,” he said.
The torrent of off-label semaglutide use among people who turn to the medication for cosmetic weight loss may intensify if a high-dose pill becomes available, said A. Janet Tomiyama, a professor of psychology at the University of California, Los Angeles, who has studied eating disorders and weight stigma and expressed concern about the impact of these drugs on people’s body image. “Any time there are medications for weight loss, we know that is a tool that people can use for a disordered eating reason,” she said, pointing to laxatives and diet pills.
As popular as these medications have become, clinicians should focus on whether semaglutide, in any form, can help make a patient healthier, instead of only reducing body weight, Dr. Hagan said. “I am concerned about these medications being broadly used just to promote weight loss,” he said, “and how it contributes to our general diet culture, our cultural obsession with thinness.”
Dani Blum is a reporter for Well.