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. 2025 Aug 4:e253599.
doi: 10.1001/jamainternmed.2025.3599. Online ahead of print.

Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes: The OASIS 2 Randomized Clinical Trial

Takashi Kadowaki  1 , Line Dam Heftdal  2 , Hae-Jin Ko  3 , Maria Overvad  2 , Iichiro Shimomura  4 , Usha K Thamattoor  5 , Kyoung-Kon Kim  6 ; OASIS 2 Investigators
Collaborators, Affiliations

Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes: The OASIS 2 Randomized Clinical Trial

Takashi Kadowaki et al. JAMA Intern Med. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kadowaki reported grants and personal fees from Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co Ltd, Novo Nordisk Pharma Ltd, Mitsubishi Tanabe Pharma Corporation, Taisho Pharmaceutical Co Ltd, Sumitomo Pharma Co Ltd, Kyowa Kirin, Daiichi Sankyo, and Takeda Pharma; personal fees from MSD Corporation, Abbott Japan Ltd, Teijin Pharma Ltd, Ono Pharmaceutical Co Ltd, FUJIFILM Toyama Chemical Co Ltd, Medtronic Japan, and AstraZeneca outside the submitted work. Dr Heftdal reported nonfinancial support from OPEN Health Communications during the conduct of the study and is an employee and shareholder of Novo Nordisk outside the submitted work. Dr Ko reported grants from Novo Nordisk during the conduct of the study; grants from Boehringer Ingelheim, Huons, and Hanmi Pharma Korea; and personal fees from Novo Nordisk, Hanmi Pharma Korea, Amgen Korea, and Alvogen Korea outside the submitted work. Dr Overvad is an employee of Novo Nordisk and reported nonfinancial support from OPEN Health Communications during the conduct of the study. Dr Shimomura reported grants from Eli Lilly Japan K.K., Teijin Pharma, Mochida Pharmaceutical, Kowa, Kyowa Kirin, Sumitomo Pharma, Rohto Pharmaceutical, Kobayashi Pharmaceutical, Nissin Foods Holdings, Cancerscan, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Osaka Central Hospital, Hakuhokai Central Hospital, Midori Health Care Center, Kyowakai Medical Corporation, Ono Medical Research Foundation, Suzuken Memorial Foundation, Manpei Suzuki Diabetes Foundation, and Japan Agency for Medical Research and Development; consulting fees from Merck Sharpe & Dohme K.K., Taisho Pharmaceutical, Nippon Boehringer Ingelheim, and Novo Nordisk Pharma; and personal fees from Arcray, Merck Sharpe & Dohme K.K., Astellas Pharma, AstraZeneca K.K., Abbott Japan, Ono Pharmaceutical, Otsuka Pharmaceutical, Kyorin Pharmaceutical, Johnson & Johnson K.K., Kyowa Kirin, Kowa, Sanofi, Sumitomo Pharma, Sanwa Kagaku Kenkyusho, Teijin Pharma, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Chugai Pharmaceutical, Nipro Corporation, Eli Lilly Japan K.K., Nippon Boehringer Ingelheim, Novartis Pharma K.K., Novo Nordisk Pharma, Mochida Pharmaceutical, Bayer Yakuhin, Pfizer Japan, and Lotte outside the submitted work; participates on the advisory board for AstraZeneca K.K., Novo Nordisk Pharma, Eli Lilly Japan K.K., Amgen, Shionogi & Co., Sumitomo Pharma, and Nissin Foods Holdings; and is an unpaid member of boards for the Japan Society for the Study of Obesity, Japan Endocrine Society, Japan Diabetes Society, Japanese Society for Treatment of Obesity, Japanese Society of Molecular Medicine, Japanese Society of Internal Medicine, Japan Atherosclerosis Society, Japan Society of Metabolism and Clinical Nutrition, and Japanese Society of Anti-Aging Medicine. Dr Thamattoor is an employee of Novo Nordisk and reported nonfinancial support from OPEN Health Communications during the conduct of the study. Dr Kim reported grants from Novo Nordisk during the conduct of the study; grants from Hanmi Pharmaceutical, Alvogen Korea, Huons, Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; and personal fees from Eli Lilly Korea, Novo Nordisk, Hanmi Pharmaceutical, Alvogen Korea, and Chong Kun Dang outside the submitted work. No other disclosures were reported.

Comment in

  • doi: 10.1001/jamainternmed.2025.3618

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