Oral Semaglutide 25 mg Demonstrates Substantial Weight Loss in Adults with Overweight or Obesity: Results from the OASIS 4 Trial

The global burden of obesity continues to rise, affecting quality of life, increasing healthcare costs, and contributing to major chronic diseases such as type 2 diabetes and cardiovascular disease. Despite the widespread availability of lifestyle interventions, many individuals struggle to achieve and maintain weight loss. Pharmacologic therapies are increasingly recognized as essential tools to support long-term weight management.

Glucagon-like peptide-1 receptor agonists have transformed the treatment landscape for obesity. Until recently, these therapies were only available as subcutaneous injections. The OASIS 4 trial, published in the New England Journal of Medicine, offers important new evidence for an oral formulation of semaglutide at a dose of 25 milligrams daily.

Study Design and Population

OASIS 4 was a randomized, double-blind, placebo-controlled trial conducted across 22 sites in Canada, Germany, Poland, and the United States. A total of 307 adults without diabetes were enrolled. Eligible participants had a body mass index of 30 or greater, or 27 or greater with at least one obesity-related complication. Participants were assigned in a two-to-one ratio to receive either oral semaglutide 25 milligrams once daily or placebo, alongside standardized lifestyle interventions that included diet and physical activity counseling.

Key Findings

Over the course of 64 weeks, participants receiving oral semaglutide lost an average of 13.6 percent of their baseline body weight, compared with 2.2 percent in the placebo group. This resulted in an absolute difference of 11.4 percentage points. The proportion of participants achieving clinically meaningful weight reduction was also significantly higher with semaglutide:

• 79 percent achieved at least 5 percent weight loss
• 63 percent achieved at least 10 percent
• 50 percent achieved at least 15 percent
• 30 percent achieved at least 20 percent

These outcomes were accompanied by significant improvements in physical function, as measured by a validated quality-of-life tool. Over half of those receiving semaglutide reported clinically meaningful improvement in their ability to perform physical activities. Cardiometabolic risk factors, including waist circumference, insulin resistance, triglycerides, and inflammatory markers, also improved significantly.

Among participants with prediabetes at baseline, 71 percent reverted to normoglycemia by week 64. This finding suggests the potential of semaglutide to alter the trajectory of metabolic disease in high-risk individuals.

Safety Profile

Adverse events were consistent with the known safety profile of glucagon-like peptide-1 receptor agonists. Gastrointestinal symptoms, including nausea and vomiting, were the most common but were generally mild, transient, and self-limited. Approximately 7 percent of participants discontinued treatment due to side effects. No deaths were reported, and serious adverse events were infrequent.

Clinical Implications

The findings from OASIS 4 demonstrate that oral semaglutide at a daily dose of 25 milligrams offers a meaningful alternative to subcutaneous formulations for patients seeking a noninjectable option for weight management. The observed weight loss was similar in magnitude to that reported with higher doses of oral semaglutide and with the approved subcutaneous formulation. Importantly, the trial population was representative of individuals encountered in routine clinical care.

As obesity management continues to evolve, expanding the range of effective delivery methods will be critical to improving adherence and access. Oral agents may be preferable for individuals who are hesitant to initiate injectable therapies, or for health systems where refrigeration and cold-chain logistics pose barriers.

Conclusion

OASIS 4 confirms the efficacy of oral semaglutide 25 milligrams in producing clinically significant weight loss and improving obesity-related outcomes. Its availability may increase flexibility in treatment strategies and broaden access to pharmacologic obesity care. As healthcare systems respond to the rising prevalence of obesity, such options will be vital for comprehensive, long-term disease management.