Oral Semaglutide Cuts Body Weight 14% in East Asian Adults With Obesity

Obesity and overweight carry heightened cardiometabolic risk for East Asian individuals, who develop type 2 diabetes and related complications at substantially lower body mass index (BMI) thresholds than European populations. Despite this, large-scale weight-management trials have historically underrepresented East Asian participants. The OASIS 2 trial was designed specifically to fill this evidence gap by evaluating oral semaglutide — the first GLP-1 receptor agonist available in pill form — in a Japanese and South Korean population with overweight or obesity, approximately one-quarter of whom also had type 2 diabetes.

OASIS 2 was a 68-week multicenter, double-blind, placebo-controlled phase 3a randomized clinical trial conducted at sites in Japan and South Korea between November 2021 and September 2023. Eligible adults had a BMI of 27.0 or greater with two or more weight-related complications, or a BMI of 35.0 or greater with at least one complication. Of 201 randomized participants (mean age 49 years; mean body weight 91.9 kg; 43.3% female; 25.4% with type 2 diabetes), 134 were assigned to semaglutide 50 mg once daily and 67 to placebo, both alongside standardized lifestyle recommendations. The 2:1 allocation maximized efficacy data collection in this relatively small trial.

On the coprimary endpoint of percentage change in body weight from baseline, semaglutide produced a mean reduction of 14.3% versus 1.3% for placebo (estimated treatment difference −13.07 percentage points; 95% CI, −15.61 to −10.52; P < .001). The second coprimary endpoint — the proportion achieving ≥5% body weight loss — was met by 84.3% of semaglutide recipients versus 17.2% on placebo (odds ratio 23.00; 95% CI, 10.28–51.42; P < .001). Notably, these weight-loss magnitudes are larger than those reported in the original OASIS 1 trial conducted in non-Asian populations, consistent with prior observations that East Asian individuals tend to respond more robustly to GLP-1 receptor agonists on a relative-weight basis.

Beyond weight, oral semaglutide produced broad cardiometabolic benefits. Waist circumference, blood pressure, fasting plasma glucose, glycated hemoglobin (HbA1c), and lipid profiles all improved meaningfully compared with placebo. In the subgroup with type 2 diabetes, glycemic improvements were particularly notable, suggesting dual utility of the drug for both weight and glycemic management in this population. Physical function assessments also trended favorably in the semaglutide arm, though the trial was not powered for these secondary endpoints individually.

The safety profile aligned with the established GLP-1 receptor agonist class. Gastrointestinal adverse events were the most common, reported by 63.4% of participants on semaglutide versus 34.8% on placebo — primarily nausea, vomiting, and diarrhea. However, treatment discontinuation due to adverse events occurred in only 4.5% of the semaglutide group (6 of 134 participants), suggesting the side effects were generally manageable. No new safety signals emerged.

The trial has important limitations: it was relatively small (n=201), conducted at a single regional level (Japan and South Korea only), funded entirely by Novo Nordisk, and did not include a dedicated cardiovascular outcomes analysis. The 68-week timeframe also does not address long-term durability of weight loss. Nevertheless, OASIS 2 provides the first robust, dedicated randomized evidence that oral semaglutide 50 mg produces clinically meaningful and statistically significant weight loss in East Asian adults — a population for whom obesity-related metabolic risk is high even at moderate BMI, and for whom an effective oral GLP-1 option may be especially valuable given cultural and practical barriers to injectable therapies.