Novo Nordisk’s new oral formulation of semaglutide 25 mg (Wegovy in a pill) produced a 16.6% average weight loss among adults with obesity, according to results from a newly published clinical study. The once-daily pill, developed as an alternative to the injectable version of Wegovy, helped one in three participants lose 20% or more of their body weight.
In addition to significant weight reduction, those taking oral semaglutide 25 mg experienced improvements in daily physical function, including activities such as bending, walking, standing, and overall mobility, along with better cardiovascular risk profiles. Novo Nordisk has submitted the treatment to the US Food and Drug Administration (FDA) as the first oral GLP-1 therapy for long-term weight management.2 Production of the medication is already underway at the company’s facilities in the United States.
Landmark Study Published in The New England Journal of Medicine
The OASIS 4 phase 3 trial, published in The New England Journal of Medicine, marks a major advance in Novo Nordisk’s effort to expand obesity treatment options. Conducted over 64 weeks, the study compared once-daily oral semaglutide 25 mg plus lifestyle changes with a placebo in 307 adults who were obese or overweight and had at least one weight-related condition, but did not have diabetes.
Participants who consistently adhered to treatment achieved an average weight loss of 16.6% versus 2.7% for those taking placebo. Over one-third (34.4%) lost at least 20% of their body weight compared with 2.9% in the placebo group. These outcomes were similar to previous results with injectable Wegovy.
When measured regardless of treatment adherence, average weight loss was 13.6% for the semaglutide group compared with 2.2% for placebo. In this group, nearly 30% (29.7%) of participants still lost 20% or more of their weight, compared with 3.3% for placebo. The study also confirmed improvements in cardiovascular risk markers and physical activity levels consistent with the injectable version.
Expert Perspectives on Efficacy and Potential Impact
“The oral semaglutide 25 mg data show compelling efficacy for an oral weight management medication with 16.6% weight loss and a safety and tolerability profile consistent with injectable Wegovy,” said Martin Holst Lange, chief scientific officer and executive vice president of Research & Development at Novo Nordisk. “Currently, less than 2% of individuals with obesity in the US receive obesity medication and Wegovy in a pill may also address patient preference for oral treatment. Pending FDA approval, ample supply will be available to meet the expected US demand as we hope to set a new treatment benchmark for oral weight loss medications for people with overweight or obesity.”
The OASIS 4 trial reported that gastrointestinal side effects with the oral medication were generally mild to moderate and temporary. The most common were nausea (46.6% compared with 18.6% for placebo) and vomiting (30.9% compared with 5.9% for placebo). Adverse events leading to permanent discontinuation occurred in 6.9% of participants on semaglutide and 5.9% of those on placebo. Serious adverse events were less frequent among those taking the medication (3.9%) compared with placebo (8.8%).
These findings reinforce the established safety and tolerability record of semaglutide, supported by more than 37 million patient-years of use worldwide.
Advancing Obesity Care Through Innovation
“The OASIS 4 trial results further underscore the significant impact that semaglutide can have in achieving sustainable weight loss and broader health benefits,” said Sean Wharton, lead study author and medical director of the Wharton Medical Clinic. “Oral semaglutide 25 mg builds on the proven efficacy and established safety and tolerability profile of semaglutide and represents a significant advancement in obesity treatment. People with overweight or obesity have individual preferences, and with oral semaglutide as a potential new treatment option, more of those who are not on treatment today may consider starting GLP-1 treatment.”
Novo Nordisk submitted a New Drug Application (NDA) for the once-daily Wegovy® pill to the FDA in February. The review is expected to be completed by the end of 2025.5 Currently, there are no oral GLP-1 therapies approved for weight management. If authorized, the new pill will be manufactured entirely in the United States, where production is already underway at Novo Nordisk’s expanded facility.
Inside the OASIS 4 Clinical Trial
OASIS 4 was a 64-week, randomized, double-blind, placebo-controlled phase 3 trial evaluating the efficacy and safety of once-daily oral semaglutide 25 mg in 307 adults with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbidity. People with diabetes were not included.
The study included a 12-week dose escalation phase, a 52-week treatment period, and a 7-week follow-up after treatment ended. Participants were assigned in a 2:1 ratio to either semaglutide or placebo, combined with lifestyle counseling and diet modification for the duration of the trial.
Understanding Obesity as a Chronic Condition
Obesity is a complex, chronic, and progressive disease that requires long-term management. A common misconception is that it results solely from a lack of willpower, when in reality, biological, genetic, social, and environmental factors all contribute to the difficulty of losing and maintaining weight.
About Wegovy and Its Existing Uses
Wegovy is the brand name for semaglutide 2.4 mg, which is currently available as an injection. In the European Union, Wegovy is approved as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adults with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) who have at least one weight-related condition. It is also approved for adolescents aged 12 and older with obesity and a body weight above 60 kg.
The label includes clinical data showing reductions in major cardiovascular events (MACE), improvements in symptoms related to heart failure with preserved ejection fraction (HFpEF), enhanced physical function, and less pain associated with knee osteoarthritis.
In the United States, Wegovy (semaglutide) injection 2.4 mg is approved for adults and children aged 12 and older with obesity, or adults with overweight and a related medical condition, to help reduce excess body weight and maintain weight loss. It is also indicated to lower the risk of major cardiovascular events such as death, heart attack, or stroke in adults with obesity or overweight and established heart disease.
Semaglutide injection 2.4 mg carries a Boxed Warning for possible thyroid tumors, including cancer, and should not be used by individuals with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Oral semaglutide 25 mg (Wegovy in a pill) is not yet approved in the US or Europe.
