Highlight
– Oral semaglutide 50 mg once daily led to a robust 14.3% mean body weight reduction in East Asian adults with overweight or obesity over 68 weeks.
– The therapy demonstrated significant efficacy both in participants with and without type 2 diabetes (T2D).
– 84.3% of semaglutide-treated participants achieved clinically meaningful weight loss of 5% or more versus 17.2% with placebo.
– Gastrointestinal adverse events were common but generally manageable; treatment discontinuation due to adverse events was low (4.5%).
Study Background and Disease Burden
Obesity and overweight contribute substantially to morbidity and mortality worldwide through associated cardiometabolic diseases such as type 2 diabetes, hypertension, and dyslipidemia. Notably, East Asian populations tend to develop weight-related complications at lower body mass index (BMI) thresholds compared to Western populations, highlighting the need for effective and region-specific therapeutic options. Pharmacologic interventions targeting weight reduction remain limited in this population, particularly oral agents suitable for long-term use.
Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), previously demonstrated injectable formulations’ efficacy in weight management and glycemic control. Recently, an oral semaglutide formulation showed promise but lacked robust evidence in East Asian cohorts, necessitating dedicated trials to assess efficacy, safety, and tolerability in this ethnically distinct population.
Study Design
The OASIS 2 trial was a rigorously designed, multicenter, double-blind, placebo-controlled phase 3a randomized clinical trial conducted from November 2021 to September 2023 across Japan and South Korea. The trial included 201 adult participants meeting inclusion criteria of BMI ≥27.0 with at least two weight-related complications or BMI ≥35.0 with at least one related complication.
Approximately 25% of subjects had established T2D at baseline, reflecting the target population’s real-world heterogeneity. Participants were randomized 2:1 to receive either once-daily oral semaglutide, 50 mg, or placebo, alongside standardized lifestyle recommendations, over a 68-week treatment period plus a 7-week follow-up.
The two coprimary endpoints were: 1) the percentage change from baseline in body weight and 2) the proportion of participants achieving at least a 5% weight reduction. Secondary assessments included changes in physical function and cardiometabolic risk factors, as well as safety monitoring.
Key Findings
Among 201 participants (mean age 49 years, mean weight 91.9 kg, 43.3% female, 25.4% with T2D), semaglutide treatment resulted in a mean body weight decline of 14.3% (SEM 0.8%), compared with a 1.3% (SEM 1.1%) reduction with placebo. The estimated treatment difference was -13.07 percentage points (95% confidence interval [CI], -15.61 to -10.52; P < .001), demonstrating a highly significant and clinically meaningful effect.
Additionally, 84.3% (107/127) of semaglutide-treated patients achieved ≥5% weight loss versus 17.2% (11/64) in the placebo group (odds ratio 23.00, 95% CI 10.28-51.42; P < .001).
Safety outcomes showed gastrointestinal adverse events (nausea, diarrhea, vomiting) were more frequent in the semaglutide arm (63.4%) than placebo (34.8%), consistent with the GLP-1RA class profile. However, few participants discontinued treatment due to adverse events (4.5%). No unexpected safety signals emerged, and cardiometabolic risk factors improved commensurately with weight loss.
These findings confirm oral semaglutide’s potent weight reduction capacity and acceptable safety in an East Asian population, including those with T2D, for whom weight management is particularly crucial given metabolic risks even at lower BMI thresholds.
Expert Commentary
The OASIS 2 trial provides pivotal evidence addressing a gap in obesity pharmacotherapy for East Asian patients, reinforcing the therapeutic value of oral semaglutide. Dr. Taro Kadowaki et al. – lead investigators – emphasize that their results align with previous global GLP-1RA data but importantly validate oral semaglutide’s efficacy and safety in East Asians, who exhibit distinct pathophysiological and BMI thresholds for risk.
The study’s rigorous design, duration, and inclusion of participants with T2D enhance its clinical applicability. However, longer-term follow-up and real-world studies are warranted to confirm sustained benefits and rare adverse events. Additionally, investigation into how semaglutide interfaces with dietary patterns and genetic predispositions unique to East Asia could further optimize personalized treatment approaches.
Conclusion
The OASIS 2 randomized clinical trial robustly demonstrates that once-daily oral semaglutide 50 mg yields significant, clinically meaningful weight loss in East Asian adults with overweight or obesity, irrespective of T2D status. Supported by an acceptable safety profile consistent with GLP-1 receptor agonists, oral semaglutide emerges as a vital tool in combating rising obesity prevalence and related complications in this high-risk population. Further research to confirm long-term safety, adherence, and cardiometabolic outcomes will help integrate this therapy into comprehensive obesity management guidelines.
References
1. Kadowaki T, Heftdal LD, Ko HJ, Overvad M, Shimomura I, Thamattoor UK, Kim KK; OASIS 2 Investigators. Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes: The OASIS 2 Randomized Clinical Trial. JAMA Intern Med. 2025 Aug 4:e253599. doi: 10.1001/jamainternmed.2025.3599. Epub ahead of print. PMID: 40758358; PMCID: PMC12322823.
2. World Health Organization. Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed June 2025.
3. Kanaya AM, Wassink AM, Herrington D. Differences in obesity and metabolic risk factors by ethnicity. Curr Opin Lipidol. 2021;32(5):353-361. doi:10.1097/MOL.0000000000000783
4. Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.
5. Davies MJ, Bergenstal R, Bode B, et al. Efficacy of once-weekly semaglutide vs placebo as add-on to diabetes treatment over 2 years: SUSTAIN 6 trial extension. Lancet Diabetes Endocrinol. 2020;8(8):621-633.
