Kadowaki Takashi, Heftdal Line Dam, Ko Hae-Jin, Overvad Maria, Shimomura Iichiro, Thamattoor Usha K, Kim Kyoung-Kon
Toranomon Hospital, Tokyo, Japan.
Novo Nordisk, Søborg, Denmark.
JAMA Intern Med. 2025 Aug 4. doi: 10.1001/jamainternmed.2025.3599.
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.
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.
Participants were assigned 2:1 to once-daily oral semaglutide, 50 mg, or placebo, plus lifestyle recommendations, for 68 weeks.
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.
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.
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.
ClinicalTrials.gov Identifier: NCT05132088.
口服司美格鲁肽50毫克在东亚人群（其中包括2型糖尿病患者）中的疗效和安全性目前尚不清楚，该人群在较低体重指数（BMI，计算方法为体重千克数除以身高米数的平方）阈值时就比其他种族更容易出现与体重相关的并发症。
评估每日一次口服司美格鲁肽50毫克治疗东亚有或无2型糖尿病个体超重和肥胖的疗效和安全性。
设计、地点和参与者：OASIS 2试验是一项为期68周（加7周随访）的多中心、双盲、安慰剂对照3a期随机临床试验，于2021年11月至2023年9月在日本和韩国进行。纳入了BMI为27.0或更高且有2种或更多相关并发症的成年人，或BMI为35.0或更高且有1种或更多相关并发症的成年人。计划约25%的参与者在筛查时有2型糖尿病。数据于2022年3月至2025年7月进行分析。
参与者按2:1分配接受每日一次口服司美格鲁肽50毫克或安慰剂，并给予生活方式建议，为期68周。
共同主要终点是体重相对于基线的百分比变化以及体重减轻5%或更多的参与者比例。还评估了身体功能、心血管代谢危险因素和安全性的变化。
总体而言，201名参与者（平均[标准差]年龄，49[11]岁；平均[标准差]体重，91.9[18.2]千克；87名[43.3%]为女性；51名[25.4%]有2型糖尿病）被随机分配至司美格鲁肽组（n = 134）或安慰剂组（n = 67）。司美格鲁肽组体重的平均（标准误）百分比变化为-14.3%（0.8），而安慰剂组为-1.3%（1.1）（估计治疗差异为-13.07个百分点；95%置信区间，-15.61至-10.52；P <.001）。与安慰剂相比，司美格鲁肽组有更多参与者体重减轻5%或更多（127名中的107名[84.3%]对64名中的11名[17.2%]；优势比，23.00；95%置信区间，10.28 - 51.42；P <.001）。134名服用司美格鲁肽的参与者中有85名（63.4%）报告了胃肠道不良事件，66名服用安慰剂的参与者中有23名（34.8%）报告了此类事件。不良事件导致司美格鲁肽组134名参与者中有6名（4.5%）停药。
在这项随机临床试验中，在东亚有或无2型糖尿病的超重或肥胖成年人中，口服司美格鲁肽50毫克与安慰剂相比导致体重有显著且具有临床意义的减轻，安全性与胰高血糖素样肽-1受体激动剂类药物一致。
ClinicalTrials.gov标识符：NCT05132088。
