(CSN)- Jared Holz considered using one of the new GLP-1 drugs for weight loss for several months before finally deciding to fill the prescription. Even after he got the medication, he hesitated for another month before starting the treatment.
One of the main reasons for his delay was his fear of needles. All the GLP-1 drugs that have been approved for weight loss come in the form of injections that people must give themselves once a week, which made him uncomfortable.
“This process has been quite difficult,” said Holz, who is 44, about a week after beginning the treatment. Despite the challenges, he pushed through, knowing it could help him with his weight loss goals.
The need for injections might soon be a thing of the past. There are at least a dozen experimental weight-loss drugs being developed in pill form, with some of the most advanced ones already in the final stages of testing.
These pills could “completely change the way we manage weight,” said Dr. Jody Dushay, an assistant professor of medicine at Harvard Medical School and a physician in endocrinology at Beth Israel Deaconess Medical Center. She regularly prescribes weight-loss medications.
The weight-loss field is already evolving rapidly, with millions of people in the US using semaglutide and tirzepatide, known as Wegovy and Zepbound for weight loss, and Ozempic and Mounjaro for diabetes.
Dushay believes that oral versions of GLP-1 drugs could help reduce shortages, lower costs, and make taking the medication more convenient. However, she and other doctors are concerned that pills could be misused, as taking daily pills might make it easier for people to take too much or share them with others.
“There’s still a lot to learn about the pill versions,” Dushay added.
Semaglutide in a pill
The most advanced of these pills include a form of semaglutide, the active ingredient in Ozempic and Wegovy, being developed by Novo Nordisk. The Danish drugmaker reported last year that a late-stage study in people who don’t have diabetes showed that the daily pill led to an average weight loss of 15% over 68 weeks, a similar result as seen in trials of Wegovy.
Novo Nordisk has not confirmed whether it has filed for approval of its new drug with the US Food and Drug Administration. Meanwhile, sales of its oral semaglutide for type 2 diabetes, known as Rybelsus, have been much lower than the injectable version, Ozempic.
Although Rybelsus is a pill, it has its own challenges. It must be taken daily on an empty stomach, and patients need to avoid eating, drinking, or taking other medications for at least 30 minutes. Some doctors also believe it may not be as effective as injections, and it still has side effects.
Dr. Jorge Moreno, an obesity specialist at Yale, explained that the dose of oral semaglutide for weight loss is much higher, ranging from 25 to 50 milligrams a day, compared to 14 milligrams for Rybelsus and 2.4 milligrams per week for the injectable Wegovy. This could mean more noticeable side effects.
“I’ve seen more significant gastrointestinal side effects with the oral version than with the injections,” Moreno said, adding that he is curious to see how the higher doses might affect patients compared to the injectable form.
Novo Nordisk reported that in its trials, most side effects of the oral drug were mild to moderate and improved over time. Like other GLP-1 medications, side effects such as nausea, vomiting, and abdominal pain are possible, though not everyone experiences them.
‘Maintenance dosing’
Not all of these experimental drugs are guaranteed to reach the market, but if they do, one of their main purposes could be to help with “long-term maintenance dosing” for people who have successfully lost weight using injectable medications, according to Dushay.
She mentioned that these medications could serve as a great alternative to weekly injections. “They might not be as effective for achieving the maximum weight loss as initial treatments, but they could be very effective for maintaining weight loss, which is a different and perhaps more important goal for long-term health benefits.”
Eli Lilly is planning to explore this idea, as indicated by recent study plans posted on a federal clinical trials database. The company intends to test orforglipron for maintaining weight loss in individuals who participated in a previous Lilly trial, which compared Zepbound with Novo Nordisk’s Wegovy. The weight maintenance trial is expected to begin this month and wrap up in early 2026.
