Jared Holz, 44, thought about taking one of the new GLP-1 weight-loss drugs — the same class of drugs as Wegovy, Saxenda and Zepbound — for months before actually filling the prescription. What’s more, even when he did get the drug, he waited a month before using it.
Part of his hesitation is that he doesn’t like needles, and all of the approved weight-loss drugs in this class are injectables that people inject themselves once a week. “That’s been really challenging,” Holz says, about a week into his treatment.
But that could soon change. At least a dozen similar experimental weight-loss drugs, designed to be taken in pill form, are moving forward in clinical trials. The most advanced studies are already in the third and final phase of testing.
These drugs will likely “change the weight management landscape dramatically in a number of ways,” says Jody Dushay, an assistant professor of medicine at Harvard Medical School and an endocrinologist at Beth Israel Deaconess Medical Center who prescribes weight-loss medications.
This is a field that is already undergoing a revolution, with millions of people in the United States now using semaglutide and tirzepatide, sold as Wegovy and Zepbound for weight loss (and for diabetes as the better-known Ozempic and Mounjaro), respectively.
Dushay highlighted the hope that tablet versions of GLP-1 drugs could ease shortages, be cheaper and more convenient. But she and other doctors also warn about the potential for misuse, a problem that could become more widespread with daily tablets instead of weekly injections; they could make it easier to overuse or inappropriately share the drug.
There is still “a lot to be learned about oral versions,” Dushay said.
Semaglutide tablet
The most advanced of these pills include a form of semaglutide, the active ingredient in Ozempic and Wegovy, that is being developed by Novo Nordisk. The Danish drugmaker reported last year that a late-stage study in people without diabetes showed that the once-daily pill led to an average weight loss of 15 percent over 68 weeks, a result similar to that seen in the Wegovy trials.
But Novo Nordisk declined to say whether it had already applied for approval of the drug from the U.S. Food and Drug Administration, and sales of an oral form of semaglutide for type 2 diabetes, approved as Rybelsus, have been surpassed by those of the injectable Ozempic.
Although it’s a pill, Rybelsus also has some challenges: It must be taken daily on an empty stomach, without eating, drinking, or taking other medications for at least 30 minutes, and doctors report that it may not be as effective as injections, and it can still have side effects.
Additionally, the oral semaglutide dose for obesity is much higher, which may increase the risk of more pronounced side effects, according to Jorge Moreno, an obesity expert and assistant professor of medicine at Yale School of Medicine. The weight-loss dose is 25 to 50 milligrams per day, compared with 14 milligrams for Rybelsus and a maximum of 2.4 milligrams per week for Wegovy injections.
“I have seen more significant gastrointestinal side effects with oral semaglutide than with the injectable,” Moreno says, noting that he wonders “what differences in side effects might occur when using such high doses of semaglutide compared to the injectable dose.”
In the trial, Novo Nordisk said the “vast majority” of side effects from oral semaglutide were “mild to moderate and decreased over time.” All GLP-1 drugs are associated with side effects such as nausea, vomiting and abdominal pain, although not all patients experience them.
Race for oral GLP-1
Following oral semaglutide is a group of drugs led by Eli Lilly’s orforglipron, an oral drug that also targets GLP-1, a hormone implicated in regulating insulin, appetite and digestion.
Lilly, which also makes Zepbound and Mounjaro, reported last year that a mid-stage trial found that people who took orforglipron for 36 weeks lost an average of 15% of their body weight — about the same amount as oral semaglutide in less time. Results from a late-stage study are expected in the first half of next year, according to Evan Seigerman, a research analyst at financial firm BMO Capital Markets.
Drugmakers like Pfizer and Roche, as well as smaller companies like Structure Therapeutics, Terns Pharmaceuticals and Viking Therapeutics, also have oral weight-loss drugs in early stages of development, according to BMO research.
Novo Nordisk isn’t stopping with semaglutide; it has several programs in early stages of development to bring next-generation weight-loss pills to market.
Earlier this month, data Research presented at the European Association for the Study of Diabetes conference showed that study participants who received a higher dose of the experimental drug amycretin lost an average of 13 percent of their body weight in 12 weeks. The drug targets both GLP-1 and another hormone, amylin.
Novo Nordisk also agreed in spending up to $1.1 billion last year to acquire Inversago Pharma, gaining an experimental oral drug called monlunabant, designed to block a receptor cannabinoids important in regulating appetite. Results from a mid-stage study of the drug are expected this year, according to BMO research.
“Maintenance dose”
Not all of these experimental drugs will necessarily make it to market, but one of the main roles they could play if they do is as a “long-term maintenance dose” for people who have lost a significant amount of weight with injectable drugs, Dushay says.
The medications could provide “an excellent alternative to weekly injections,” Dushay says. “They may not be as effective for maximal weight loss as initial therapy, but they may be excellent for weight loss maintenance, which is a different and arguably much more important goal for long-term health benefits.”
Eli Lilly will test just that, according to study plans recently posted to a federal clinical trials database. The company plans to test orforglipron for weight loss maintenance in people who participated in another Lilly’s essaycomparing its drug Zepbound with Novo Nordisk’s Wegovy. The weight maintenance trial was scheduled to begin this month and be completed in early 2026.
Holz, who closely follows the weight-loss drug race in his role as a health strategist at an investment firm, says he hopes to switch to an oral option instead of the injectable drug he’s taking weekly now, if one becomes available, to maintain his weight loss.
In three months, Holz says he has lost just over 10 percent of his body weight, and he is excited about GLP-1 drugs not only for weight loss, but also for their heart-protective effects and other potential health benefits.
The weekly injection he had been wary of turned out to be nearly painless, the strategist said — something the drug’s makers have worked to achieve with autoinjector pens — and, looking back, he wishes he had started sooner.
This content was originally published in Weight loss pills can facilitate obesity treatment; find out more on the CNN Brasil website.
Source: CNN Brasil

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