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    Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes

    JAMA Internal Medicine. October 2025: 185(10):1206-1217

    Importance

    The efficacy and safety of oral semaglutide, 50 mg, in an East Asian population that also includes individuals with type 2 diabetes (T2D), who are prone to weight-related complications at lower body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) thresholds than other ethnic groups, is currently unknown.

    Objective

    To assess the efficacy and safety of once-daily oral semaglutide, 50 mg, for the treatment of overweight and obesity in East Asian individuals with or without T2D.

    Design, Setting, and Participants

    The OASIS 2 trial was a 68-week (plus 7 weeks of follow-up) multicenter, double-blind, placebo-controlled phase 3a randomized clinical trial conducted from November 2021 to September 2023 in Japan and South Korea. Adults with a BMI of 27.0 or greater with 2 or more related complications or a BMI of 35.0 or greater with 1 or more related complications were enrolled. Approximately 25% of participants were planned to have T2D at screening. Data were analyzed from March 2022 to July 2025.

    Interventions

    Participants were assigned 2:1 to once-daily oral semaglutide, 50 mg, or placebo, plus lifestyle recommendations, for 68 weeks.

    Main Outcomes and Measures

    The coprimary end points were percentage change in body weight from baseline and the proportion of participants who achieved 5% or greater body weight reductions. Changes in physical function, cardiometabolic risk factors, and safety were also evaluated.

    Results

    Overall, 201 participants (mean [SD] age, 49 [11] years; mean [SD] body weight, 91.9 [18.2] kg; 87 [43.3%] female; 51 [25.4%] with T2D) were randomized to semaglutide (n = 134) or placebo (n = 67). The mean (SEM) percentage change in body weight was −14.3% (0.8) with semaglutide vs −1.3% (1.1) with placebo (estimated treatment difference, −13.07 percentage points; 95% CI, −15.61 to −10.52; P < .001). More participants had 5% or greater body weight reductions with semaglutide vs placebo (107 of 127 [84.3%] vs 11 of 64 [17.2%]; odds ratio, 23.00; 95% CI, 10.28-51.42; P < .001). Gastrointestinal tract adverse events were reported by 85 of 134 participants (63.4%) with semaglutide and 23 of 66 with placebo (34.8%). Adverse events led to treatment discontinuation in 6 of 134 participants (4.5%) in the semaglutide arm.

    Conclusions and Relevance

    In this randomized clinical trial, among East Asian adults with overweight or obesity, with or without T2D, oral semaglutide, 50 mg, led to a superior and clinically meaningful reduction in body weight compared with placebo, with a safety profile consistent with the glucagon-like peptide-1 receptor agonist class.

    Trial Registration

    ClinicalTrials.gov Identifier: NCT05132088