10/26/2025
Obesity Drug Battleground: Wins for Clinicians and Patients?
The race for the weight-loss drug market is intensifying as Eli Lilly and Novo Nordisk compete to capture market share — and the winners may well be clinicians and patients.
“The rivalry is good for patients, and it’s good for the field because it’s stimulating the development of new treatments and therefore, more choices and potentially more efficacy and fewer side effects,” Louis J. Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, told Medscape Medical News.
Lilly produces tirzepatide (Zepbound for obesity and Mounjaro for type 2 diabetes [T2D]), and Novo Nordisk produces semaglutide (Wegovy for obesity and Ozempic for T2D). For obesity, both drugs are given by weekly injection, and both companies are seeking approval for oral weight-loss formulations to be administered daily.
Recent studies between the two competitors include a head-to-head comparison of their injectables for obesity (tirzepatide came out ahead) and randomized, placebo-controlled trials of oral formulations of orforglipron (Lilly) and semaglutide in people who have overweight or obesity. Approvals of these formulations could potentially broaden the market to include those who prefer pills to injections. Although oral semaglutide (Rybelsus) is already available as a daily pill, it is approved only for managing T2D, and the dose is lower than that of the oral weight-loss formulation.
Aronne, who led the comparative injectable study, recently spoke with a patient who “did incredibly well on one of the injectables, but they’re starving now.” Another patient took one and now “can’t eat a thing.” Therefore, although both drugs work well overall, he said, “We still have people who don’t respond to them, and so we need a lot of different treatments, and the competition between companies will give us that.”
Insurance, Complications, Cost
Does the rivalry between companies affect how clinicians are prescribing for patients? For the currently available injectables, probably not, at least for now, according to interviewees. “I hate to say it, but the key factor in our describing decisions is insurance,” Aronne said. “If one drug is covered and the other isn’t, we will go with the one that’s covered.”
That approach probably works for the majority of patients, he said. “Although we know from the comparison study that [tirzepatide] is more effective for weight loss than semaglutide, the reality is, not everyone needs that level of efficacy. People can do just fine on a drug that might be less efficacious. So we try one and see how the patient does, and if they do well, great, they just stay on that one. If not, we’ll switch them over to the other one. It’s pretty much trial and error.”
Obesity complications are also a factor, he said. If the patient has sleep apnea, then most likely tirzepatide will be prescribed because it is FDA-approved for treating sleep apnea as well as weight. Similarly, if the patient is at risk for stroke or other serious cardiovascular events, then semaglutide, which is indicated to reduce those risks, would be prescribed.
“If a patient has osteoarthritis, we might prescribe [semaglutide],” which has been shown to improve pain and function, Aronne said. And “both drugs have been shown to be effective in reducing fatty liver, so we know either will help. Therefore, management of the underlying complications plays an important role in our prescribing decisions.”
This means companies are likely scurrying for new indications for their drugs, “and that’s good for patients because the drugs will show additional benefits, and we should wind up with more and more insurance coverage,” he said.
Ajaykumar Rao, MD, chief of endocrinology, diabetes, and metabolism at the Lewis Katz School of Medicine at Temple University in Philadelphia, agreed. Clinicians should review each drug’s prescribing insert to determine which was approved for specific clinical indications, he told Medscape Medical News.
Will Costs Go Down?
Whether the rivalries could lead to lower costs and/or greater access is an open question at this point. “When there is direct competition between manufacturers of similar medications, patients can benefit, as this may also drive more competitive pricing and incentives/discount programs,” said American Gastroenterological Association spokesperson Carolyn Newberry, MD, also of Weill Cornell Medicine.
“However, this usually only drives prices down after the drugs go generic, with more mixed results on pricing under brand-name distribution,” she told Medscape Medical News.
“Since the Lilly molecule doesn’t require an injector pen or refrigeration, and it can be manufactured more easily, there is an expectation that it may be sold at a lower price,” said Sriram Machineni, MD, director of the Fleischer Institute Medical Weight Center at Montefiore Einstein in the Bronx, New York. “However, this may not come to pass, as it will be the first drug of its kind.”
“The biggest hurdle for the adoption of either of these medications is likely to be the stance that many insurance companies take,” he told Medscape Medical News. “They view obesity as a disease that isn’t serious on its own and so are often reluctant to cover treatments for it. Conversely, these same insurance companies would not hesitate to cover the same medication if it were prescribed for T2D.”
How Might Oral Formulations Change Prescribing?
Newberry believes the availability of oral obesity medications will likely affect prescribing habits because patients will have more options. “Considerations will include a patient’s preference between oral and injectable administration, balancing other factors such as dosing frequency (daily vs weekly), insurance coverage, tolerance, and required weight loss to achieve personal health benefits.”
Of note, she added, “These new daily higher-potency oral alternatives to weekly subcutaneous injectables still produce less weight loss overall than currently available drugs and are dosed more frequently. Their ramp-up periods are also different. Side effect profiles are still being teased out, and larger head-to-head trials will be needed to assess differences.”
“My decision will be based on the characteristics of the medications,” Machineni said. For example, patients taking semaglutide 25 mg will need to do so on an empty stomach with 4 ounces of water and can’t exercise for at least 30 minutes after taking it. “On the other hand, orforglipron does not have these restrictions and can be taken at any time with food, which offers more flexibility in administration and is better suited for patients who are less reliable with their medication schedule,” he said.
Effects on obesity complications would also be a factor, as they are for the injectables. “Injectable semaglutide has been shown to reduce the risk of heart disease, and there is hope that the oral version will offer similar benefits,” said Machineni. “However, the cardiovascular protection of orforglipron remains unknown. Therefore, if a patient has a history of heart attack or stroke and is looking for an oral agent, I may recommend semaglutide.”
Oral semaglutide has an advantage in that it’s the same molecule that’s in the injectable formulation and therefore has over 7 years of use, Aronne noted. “That means we have a lot of evidence supporting its safety and the side effect profile.”
“In addition, we know that semaglutide acts specifically on the GLP-1 receptor, and we know its effects in the millions of people who have taken it,” he said. By contrast, orforglipron is a new chemical entity, and although it’s been studied in thousands of people, it might still have off-target effects.
“We like to think it’s going to just hit the receptor, but we’re not sure, and that’s something that also needs to be taken into consideration when deciding which pill to prescribe,” he explained.
In a similar vein, Rao noted, “I think it is great to have more options that are noninjectable, and I would say [the two products] appear to be comparable, but we will have to see how that plays out practically.”
When will that be? At press time, a Novo Nordisk spokesperson told Medscape Medical News that the FDA is expected to respond to the request for approval in Q2025, and the company “cannot comment on price at this point.”
The latest announcement on the Lilly website says that submissions for approval for orforglipron are planned to begin in late 2025 and 2026 and that “pricing will reflect the medicine’s value and aims to ensure it is accessible to those who need it.”
Aronne disclosed being a consultant, speaker, and advisor for and receiving research support from Altimmune, Amgen, AstraZeneca, Eli Lilly and Company, Intellihealth, Janssen, Novo Nordisk, Pfizer, Senda, UnitedHealth Group, Versanis, and others. He reported having ownership interests in ERX, Intellihealth, Jamieson, Kallyope, Skye Bioscience, Veru, and others, and is also reported serving on the board of directors of ERX, Jamieson Wellness, and Intellihealth/FlyteHealth.
Newberry declared receiving consulting fees from Eli Lilly and Company in the past. Machineni reported being involved in semaglutide and tirzepatide clinical trials and reported being a consultant to Novo Nordisk, Eli Lilly and Company, and Rhythm Pharmaceuticals. Rao declared having no relevant disclosures.
Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.
