Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes
Takashi Kadowaki, Line Dam Heftdal, Hae‐Jin Ko, Maria Overvad, Iichiro Shimomura, Usha K. Thamattoor, Kyoung Kon Kim, OASIS 2 Investigators, H Kunishige, Jun Okude, Naoki Sato, Satoshi Takeda, Koji Uemura, Takeshi Osonoi, Satomi Isshiki, Naoaki Ito, Hitoshi Naito, Norihiko Oka, Mitsuru Hosoya, Miyoko Saito, H Takizawa, Hiroshi Asano, Shinichiro Shirabe, Taro Asakura, Mizuki Kaneshiro, Hitoshi Matsuura, Akeo Ohira, Saburo Nakano, Yasumichi Mori, Kimio Matsumura, Kaoru Nagasawa, Takashi Kadowaki, Takayasu Uchida, Shota Kikuno, Yuya Suzuki, Shizuka Kaneko, Haruhiko Onaka, Y Ueba, Yoshiyuki Onda, Tomoko Minami, Tomoaki Osugi, Shinsuke Tokumoto, Kazuya Motohashi, Mutsumi Okada, Nao Machida, Shun Kizawa, Hitoshi Nishizawa, Norikazu Maeda, Iichiro Shimomura, Yuya Fujishima, Shiro Fukuda, Hirotaka Nagashima, Yoshimasa Horie, Takako Ohyama, Kazuki Yoshida, Asaji Yamamoto, Akiko Kishi, K Soeda, Hayato Fujita, Aki Tsuji, Yuichi Takahashi, Satoshi Inoue, Michio Yagi, Yasuko Owada, Shigeto Kanada, Hidetoshi Furuie, Yasuhiko Suga, Takuya Inomoto, Daiki Yamaguchi, Kayo Yoshida, Kenichi Yamahara, Masanobu Nanto, Sumiko Kobayashi, Yuko Soma, Osamu Matsuoka, Makoto Kawai, Mie Kawai, Miki Ito, Izumi Yamaguchi, Hideki Matsuda, Sachiko Otake, Eunju Sung, In Young Cho, H.E. Yoon, HyunJun Kang, Kyoung Kon Kim, Hae-Jin Ko, Hee-Eun Hong, Ju Young Kim, Hye Yeon Koo, S.-H. Lee, Eun-byul Cho, MunYoung Yoo
Abstract
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.