A cross-trial comparison shows Novo's oral semaglutide produced three percentage points more weight loss and fewer dropouts due to side effects
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Novo Nordisk published a cross-trial comparison claiming its Wegovy pill produced greater weight loss than Eli Lilly $LLY's newly approved obesity tablet Foundayo, raising the stakes as the two companies compete to shape prescribing trends in the oral GLP-1 market.
The comparison found that Novo's 25 mg dose of oral semaglutide caused 3.2 percentage points more weight loss than Lilly's 36 mg orforglipron — regardless of whether patients stayed on treatment. The study also found that patients on orforglipron, under the brand name Foundayo, had roughly 14 times the odds of stopping treatment due to gastrointestinal side effects compared with those on the Wegovy pill, and roughly four times the odds of discontinuing due to any adverse event.
The study, called ORION, was a population-adjusted indirect treatment comparison using data from Novo and Lilly's separate phase 3 clinical trials. It was not a head-to-head trial and did not include new clinical data. Novo said it will present the full findings at the Obesity Medicine Association's annual conference in San Diego on April 10.
Novo acknowledged several limitations. Researchers adjusted for baseline body weight, sex, and glycemic status, but noted that other unaccounted factors may remain. Differences in how the two trials were designed could also affect comparability. Given the low number of adverse events counted, the company cautioned that the tolerability findings should be interpreted carefully.
"Since there are no head-to-head trials comparing oral semaglutide for obesity to orforglipron, this indirect treatment comparison from the ORION study provides important information that can be used during the shared decision-making process," Robert F. Kushner of Northwestern Feinberg School of Medicine said in a statement.
In a separate preference study, four out of five respondents, or 84% of the 800 U.S. adults surveyed, said they would choose Wegovy's profile over Foundayo's. That study, called OPTIC, was conducted in October and November 2025, before Lilly's new product received regulatory approval. Novo noted the hypothetical profiles used may not exactly match final FDA-approved labeling.
The two pills differ in how they must be taken. Foundayo carries no food or timing restrictions. The Wegovy pill, by contrast, requires patients to consume it first thing each morning with a small sip of water and fast for at least half an hour afterward.
Lilly CEO Dave Ricks told CNBC that Foundayo's lack of dosing restrictions makes it more convenient for patients to incorporate into their day. Novo CEO Mike Doustdar dismissed concerns about those requirements in a March CNBC interview, saying it was "absolutely not the case" that they would deter patients.
The Wegovy pill debuted in the American market at the start of the year and has now reached more than 600,000 patients. The FDA approved Foundayo earlier this week through its National Priority Voucher program, 294 days ahead of its standard review deadline. The agency said it's the fastest any new molecular entity has received approval since 2002.
The companies have matched each other on entry-level pricing, setting the lowest doses at $149 a month for uninsured patients.
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