Topline findings: OASIS 4 trial
- Oral semaglutide 25 mg achieved 16.6% mean weight loss at 64 weeks with full adherence, compared with 2.7% for placebo.
- One-third of adherent participants achieved at least 20% weight loss, versus under 3% with placebo.
- Weight loss remained robust in the treatment-policy analysis, at 13.6% versus 2.2% with placebo.
- Serious adverse events occurred less frequently with oral semaglutide than placebo (3.9% vs 8.8%).
- Post hoc analyses showed improvements in glycemic control, blood pressure, and cardiovascular risk factors, including normalization of blood glucose in more than 70% of participants with prediabetes at baseline.
The FDA has approved Novo Nordisk’s Wegovy pill (semaglutide), marking the first oral GLP-1 available for weight loss in adults. Additionally, the therapy is indicated to reduce the risk of major adverse cardiovascular events including death, heart attack, or stroke.1
This regulatory action is backed by positive results from the Phase III OASIS 4 clinical trial (NCT05564117).
In a company statement, Dave Moore, executive vice president, US operations at Novo Nordisk, said: "The launch of Wegovy in 2021 changed how obesity was viewed and treated in the US. Now, with Wegovy pill, we are offering a magnitude of weight loss that no other oral GLP-1 obesity candidate has been able to duplicate in Phase III trials. We are confident that the expansion of Wegovy to a pill will help patients who may have not sought or accepted treatment before. Wegovy pill is the next chapter in our decades-long GLP-1 experience—supported by the most affordable self-pay price to date in a GLP-1 for obesity. We are prepared for a full US launch in early January 2026, with manufacturing well underway in our North Carolina facilities."
Approval based on topline findings from OASIS 4
Earlier in September, The New England Journal of Medicine published topline findings from OASIS 4.2
- With full treatment adherence, oral semaglutide 25 mg produced 16.6% mean weight loss at 64 weeks, versus 2.7% with placebo.
- 34.4% of adherent participants achieved ≥20% weight loss, compared with 2.9% on placebo.
- In the treatment-policy analysis (regardless of adherence), oral semaglutide still achieved 13.6% mean weight loss versus 2.2% with placebo.
- Nearly 30% of participants reached ≥20% weight loss in the treatment-policy analysis, compared with 3.3% on placebo.
- Serious adverse events were less frequent with oral semaglutide (3.9%) than placebo (8.8%), consistent with extensive real-world safety experience.
In a press release from the time of publication, Sean Wharton, lead study author and medical director of the Wharton Medical Clinic, said: “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.”
