The New England Journal of Medicine has published the results from Novo Nordisk’s OASIS 4 Phase 3 trial, marking a major advance in obesity treatment with the investigational once-daily oral semaglutide 25 mg (the pill version of Wegovy). The 64-week study evaluated the efficacy and safety of oral semaglutide combined with lifestyle changes in 307 adults with obesity or overweight and weight-related health issues, but without diabetes.
The trial revealed that participants who fully adhered to the oral semaglutide treatment achieved an average weight loss of 16.6%, compared to just 2.7% in the placebo group. Over a third (34.4%) of those on oral semaglutide lost 20% or more of their body weight, versus 2.9% with placebo. These results are comparable to those seen with the injectable version of Wegovy.
Even when including all participants regardless of adherence, oral semaglutide users still lost an average of 13.6% of their weight, significantly outperforming the 2.2% loss seen with placebo. Nearly 30% of participants on the drug lost 20% or more of their body weight.
Beyond weight loss, oral semaglutide also improved cardiovascular risk factors and increased patients’ ability to be active, consistent with previous data from injectable Wegovy.
Martin Holst Lange, Novo Nordisk’s Chief Scientific Officer, said, “These data show compelling efficacy for an oral weight management medication with a safety and tolerability profile consistent with injectable Wegovy. Given that fewer than 2% of Americans with obesity currently receive medication, the pill form may better meet patient preferences.”
The safety profile of oral semaglutide aligned with that of the injectable version, with mostly mild to moderate gastrointestinal side effects such as nausea (46.6% vs. 18.6% placebo) and vomiting (30.9% vs. 5.9% placebo). Serious adverse events were actually lower in the oral semaglutide group compared to placebo.
Lead study author Sean Wharton highlighted the significance of the findings, stating, “Oral semaglutide represents a major advancement in obesity treatment. Offering an oral option can help more people consider GLP-1 therapy for sustainable weight loss and health improvements.”
Novo Nordisk submitted a New Drug Application for the oral Wegovy pill in February 2025, with FDA review expected to conclude by year-end. If approved, it would be the first oral GLP-1 medication approved for weight loss, produced entirely in the U.S. at Novo Nordisk’s expanded manufacturing facility.
This milestone underscores Novo Nordisk’s commitment to expanding treatment options for the millions affected by obesity and related health conditions.