New Weight-Loss Drugs May Change Landscape for Treatment
Jared Holz, a health-care strategist from an investment firm, spent months contemplating the decision to take one of the new GLP-1 drugs approved for weight loss before finally filling the prescription. Once he had the medication, he waited an additional month before he began using it.
Holz’s reluctance stemmed from his discomfort with needles; all weight loss drugs currently approved in this category require users to administer weekly self-injections.
“This has been really challenging,” Holz, 44, said about a week into his treatment regimen.
However, changes may be on the horizon. At least a dozen experimental weight-loss drugs designed as pills are progressing through clinical trials, with some in the third and final phase of testing.
Dr. Jody Dushay, an assistant professor of medicine at Harvard Medical School and an attending physician in endocrinology at Beth Israel Deaconess Medical Center, stated, “They’re likely to drastically change the landscape for weight management in several ways.” Dushay regularly prescribes weight-loss medications and is observing the ongoing developments in this field.
The popularity of current injections, like semaglutide and tirzepatide, sold as Wegovy and Zepbound, has exploded, with millions across the United States using these medications for weight management and diabetes control, where they are more commonly recognized as Ozempic and Mounjaro.
Dushay expressed hope that oral versions of GLP-1 drugs could alleviate medication shortages, lower costs, and increase convenience for users. However, she, along with other medical professionals, raised concerns about the potential for misuse, particularly with daily pills, which might make it easier for patients to exceed recommended dosages or share their medications improperly.
“There’s a lot to be learned about the oral versions,” Dushay noted.
Among the most advanced oral drugs is a form of semaglutide developed by Novo Nordisk, which reported last year that a late-stage study indicated a daily pill led to an average weight loss of 15% over 68 weeks in non-diabetic participants, mirroring outcomes from Wegovy trials.
Still, Novo Nordisk has not revealed whether it has submitted this oral drug for approval by the U.S. Food and Drug Administration (FDA). Furthermore, although the oral semaglutide, known as Rybelsus, is available for type 2 diabetes, its sales fall short of those for the injectable Ozempic.
Rybelsus presents its own challenges; it must be consumed daily on an empty stomach, without eating, drinking, or taking other medications for at least 30 minutes. Additionally, doctors have reported that although it may not be as effective as injections, it still carries side effects.
Moreover, the dose of oral semaglutide for obesity is considerably higher—between 25 and 50 milligrams daily—compared to 14 milligrams for Rybelsus and a maximum of 2.4 milligrams weekly for Wegovy injections. Dr. Jorge Moreno, an obesity specialist and assistant professor of medicine at Yale School of Medicine, indicated that he has observed more significant gastrointestinal side effects with oral semaglutide than with its injectable counterpart.
Novo Nordisk has stated that “the vast majority” of the side effects reported from oral semaglutide are “mild to moderate and diminished over time.” Common side effects across all GLP-1 medications include nausea, vomiting, and abdominal pain, though not all patients experience these issues.
Concurrent with oral semaglutide, Eli Lilly is leading a group of drugs that includes orforglipron, which also focuses on the GLP-1 hormone, known for its role in insulin regulation, appetite, and digestion. Last year, Lilly reported that a midstage trial of orforglipron showed participants losing an average of 15% of their body weight over 36 weeks—similar to results from oral semaglutide but in a shorter timeframe. Additional results are anticipated from a later-stage study in the first half of next year, as indicated by Evan Seigerman, a research analyst at BMO Capital Markets.
Other drug manufacturers, including Pfizer, Roche, and smaller entities such as Structure Therapeutics, Terns Pharmaceuticals, and Viking Therapeutics, are also exploring oral weight-loss medications in earlier development phases, according to BMO research.
In addition, Novo Nordisk is not limiting its efforts to semaglutide alone. The company has several programs aimed at developing next-generation weight-loss pills. Recently, data presented at the European Association for the Study of Diabetes conference revealed that higher doses of an experimental drug called amycretin resulted in a 13% average weight loss over 12 weeks, targeting both GLP-1 and amylin hormones.
Furthermore, last year, Novo Nordisk committed to spending up to $1.1 billion to acquire Inversago Pharma and gain access to monlunabant, an experimental oral drug aimed at blocking a cannabinoid receptor related to appetite regulation. Midstage study results on this drug are expected this year.
Dushay suggests that if these experimental drugs reach the market, they may primarily serve as “long-term maintenance dosing” for those who have lost a significant amount of weight on injectable therapies. She noted, “They may not be as effective for maximum weight loss as initial therapy but could be excellent for weight-loss maintenance, which is a different and arguably much more important destination for lasting health benefits.”
For his part, Holz hopes to transition from his current weekly injection to an oral option for maintaining his weight loss, should one become available. Over the past three months, he reported a weight loss of just over 10% and expressed enthusiasm over the potential health benefits of GLP-1 drugs beyond weight loss, including their effects on heart health.
Reflecting on his initial concerns, Holz remarked that the weekly injection turned out to be nearly painless, a feat achieved by the drug’s manufacturers through the development of autoinjector pens. He concluded by expressing a wish that he had started the treatment sooner.