Once-weekly semaglutide 2·4 mg in an Asian population with obesity, defined as BMI ≥25 kg/m, in South Korea and Thailand (STEP 11): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Consistent with WHO recommendations, obesity is defined as BMI ≥25 kg/min many Asian populations because of increased health risks at lower BMIs than in other populations. We aimed to investigate the efficacy and safety of once-weekly subcutaneous semaglutide 2·4 mg versus placebo in an Asian population with BMI ≥25 kg/m, together with lifestyle interventions. METHODS: STEP 11 was a 44-week, randomised, double-blind, placebo-controlled, phase 3 trial conducted at 12 clinical sites in South Korea and Thailand. Adults (aged ≥18 years in Thailand and ≥19 years in South Korea) with obesity (BMI ≥25 kg/m) of Asian descent, without diabetes, were randomly assigned 2:1 with a computer-generated sequence and block randomisation to once-weekly subcutaneous semaglutide 2·4 mg or placebo, with a reduced-calorie diet and increased physical activity. Participants, care providers, investigators, and assessors were masked to allocation. Coprimary endpoints, measured in all randomly assigned participants by intention to treat, were percentage bodyweight change and the proportion of participants reaching ≥5% bodyweight reduction. Confirmatory secondary endpoints were the proportion of participants with ≥10% and ≥15% bodyweight reductions and change in waist circumference. Safety was assessed via the assessment of adverse events in all participants who received at least one dose of semaglutide or placebo. This trial was registered at ClinicalTrials.gov (NCT04998136). FINDINGS: Between Aug 15, 2022, and Nov 20, 2023, 150 participants were randomly assigned (101 to semaglutide 2·4 mg and 49 to placebo). Six (6%) in the semaglutide group and two (4%) in the placebo group discontinued treatment before week 44. 111 (74%) were female and 39 (26%) male, with a mean age of 39 years (SD 11), mean bodyweight of 83·8 kg (18·1), and mean BMI of 31·3 kg/m(5·2). At week 44, mean change in bodyweight was -16·0% (SE 0·7) in the semaglutide 2·4 mg group versus -3·1% (0·9) in the placebo group (p<0·0001), and a greater proportion of participants reached bodyweight reductions of ≥5% (96 [96%] vs 12 [25%]; p<0·0001), ≥10% (78 [78%] vs 5 [10%]; p<0·0001), and ≥15% (53 [53·0%] vs 2 [4·2%]; p<0·0001) in the semaglutide 2·4 mg group. Mean change in waist circumference was -11·9 cm (SE 0·7) with semaglutide versus -3·0 cm (1·0) with placebo (p<0·0001). Adverse events were reported by 90 (89%) of 101 participants in the semaglutide 2·4 mg group and 38 (78%) of 49 participants in the placebo group, with 13 (13%) reporting serious adverse events in the semaglutide 2·4 mg group versus four (8%) in the placebo group. Gastrointestinal adverse events were the most common adverse events in participants in the semaglutide group. INTERPRETATION: In this Asian population with obesity (BMI ≥25·0 kg/m), once-weekly semaglutide 2·4 mg significantly reduced bodyweight and was well tolerated. The results have meaningful clinical and policy implications for Asian countries, where lower BMI thresholds are used to define obesity compared with other populations. The efficacy and safety of semaglutide 2·4 mg support its inclusion in local treatment guidelines. These findings might also inform reimbursement policies and national obesity strategies, highlighting the importance of population-specific approaches. FUNDING: Novo Nordisk. TRANSLATIONS: For the Thai and Korean translations of the abstract see Supplementary Materials section.