Landmark OASIS 2 Trial: Oral Semaglutide Delivers Significant Weight Loss and Metabolic Benefits in East Asian Adults

Obesity and its metabolic complications are surging across Asia, with unique clinical challenges for East Asian populations, including developing type 2 diabetes (T2D) and cardiovascular disorders at lower BMI thresholds than in Western countries. To address gaps in tailored pharmacological therapy, researchers have assessed oral semaglutide—a glucagon-like peptide-1 (GLP-1) receptor agonist already approved for obesity—in a population-specific context.

The OASIS 2 Trial: Focused on East Asia

The OASIS 2 trial was a phase 3, multicenter, double-blind, placebo-controlled study conducted from November 2021 to September 2023 in Japan and South Korea. It enrolled 201 adults (mean age 49 years; 43% female) with overweight or obesity and at least one weight-related complication. Notably, 25% had established T2D, matching the real-world higher risk for diabetes in this population.

Participants were randomized 2:1 to once-daily oral semaglutide 50mg or placebo, both paired with lifestyle intervention (diet and exercise counseling). The trial’s primary endpoints focused on the percentage change in body weight and the proportion of participants achieving at least 5% weight reduction.

Clinically Important Weight Loss Achieved

After 68 weeks:

• Oral semaglutide resulted in a mean body weight reduction of 14.3%, compared to 1.3% with placebo. The estimated treatment difference was −13.07 percentage points (P<.001).

• 84.3% of participants receiving semaglutide lost at least 5% of their baseline body weight (vs. 17.2% with placebo).

• Substantial proportions achieved even greater reductions:

  • 65.4% lost ≥10%

  • 47.2% lost ≥15%

  • 32.3% lost ≥20%

  • By contrast, no participant in the placebo group achieved ≥15% body weight reduction.

In participants without T2D, the average weight loss with semaglutide was 15.5%. Among those with T2D, mean weight loss was 10.7%—notably matching or exceeding guideline recommendations for risk reduction in this population.

Benefits Beyond the Scale

Oral semaglutide also improved several cardiometabolic markers compared to placebo:

• Systolic blood pressure dropped by 9.4mm Hg (vs. 2.2mm Hg with placebo).

• HbA1c decreased by 0.78 percentage points (vs. an increase of 0.03 in the placebo group).

• Lipid profiles improved, with decreases in LDL and triglycerides and a reduction in high-sensitivity C-reactive protein.

• In a Japanese subpopulation undergoing CT scans, visceral fat area was reduced by 32% with semaglutide, reinforcing mechanistic benefits highly relevant to East Asian risk profiles.

Safety and Tolerability in Line with GLP-1 Class

The safety profile mirrored established data for GLP-1 receptor agonists. The most common adverse events were mild or moderate gastrointestinal complaints (nausea, constipation, diarrhea), mostly during dose escalation. Adverse events led to treatment discontinuation in 4.5% of participants in the semaglutide group versus none in the placebo group. No new safety signals emerged.

Practical Implications

These findings carry substantial clinical importance. Oral semaglutide provides an effective non-injectable treatment option for East Asian individuals with overweight or obesity, including those with T2D. The magnitude of both weight loss and metabolic improvements supports its potential as a foundational pharmacotherapy in this high-risk group—where rates of visceral fat accumulation and diabetes rise at lower BMIs.

Given that adherence and quality of life were maintained, and adverse events were manageable, oral semaglutide stands to improve real-world outcomes for millions in a region with rising obesity-related health burdens.

Conclusion
Oral semaglutide, 50mg daily, led to clinically meaningful, statistically significant weight loss and cardiometabolic risk reduction in East Asian adults with overweight or obesity—with or without T2D—compared to placebo. The results, consistent with prior global studies, confirm oral administration as a viable alternative to injectable GLP-1 agonists for this population.

For individuals and clinicians striving for better management of obesity and its complications in East Asia, oral semaglutide emerges as a promising new ally.