Introduction: Addressing the Asian Paradox in Obesity
Obesity is a global health crisis, but its clinical manifestation and associated risks vary significantly across ethnic populations. In many Asian regions, individuals experience increased metabolic health risks—such as type 2 diabetes and cardiovascular disease—at much lower body mass index (BMI) levels compared to Western populations. Consequently, the World Health Organization (WHO) and local health authorities in countries like South Korea and Thailand define obesity starting at a BMI of 25 kg/m2. While the efficacy of the GLP-1 receptor agonist semaglutide 2.4 mg has been well-established in global trials (the STEP program), there remained a critical need for high-quality, randomized controlled data specifically targeting this Asian demographic at these lower BMI thresholds. The STEP 11 trial was designed to bridge this gap.
Highlights of the STEP 11 Trial
The STEP 11 trial yielded several pivotal findings that underscore the clinical utility of semaglutide in Asian populations:
- Participants treated with once-weekly semaglutide 2.4 mg achieved a mean bodyweight reduction of 16.0% compared to only 3.1% in the placebo group over 44 weeks.
- An overwhelming 96% of the semaglutide group reached the clinically significant threshold of ≥5% bodyweight reduction.
- Over half (53%) of the participants in the semaglutide arm achieved a weight loss of ≥15%.
- Significant improvements were observed in waist circumference, with a mean reduction of nearly 12 cm in the treatment arm.
Study Design and Methodology
STEP 11 was a 44-week, randomized, double-blind, placebo-controlled, phase 3 trial conducted across 12 clinical sites in South Korea and Thailand. The study population included 150 adults (aged ≥18 in Thailand; ≥19 in South Korea) of Asian descent with a BMI ≥25 kg/m2, who did not have diabetes.
Intervention and Comparison
Participants were randomly assigned in a 2:1 ratio to receive either subcutaneous once-weekly semaglutide 2.4 mg (n=101) or a matching placebo (n=49). Both groups received lifestyle interventions, including a reduced-calorie diet and increased physical activity. The 44-week duration was chosen to assess both initial weight loss and mid-term sustainability.
Endpoints
The trial utilized two coprimary endpoints: the percentage change in bodyweight from baseline to week 44 and the proportion of participants achieving at least a 5% reduction in bodyweight. Secondary endpoints included higher weight loss thresholds (≥10% and ≥15%) and changes in waist circumference, a key indicator of visceral adiposity which is particularly relevant for metabolic risk in Asian populations.
Detailed Key Findings
The results of the STEP 11 trial were statistically significant and clinically robust across all primary and secondary metrics.
Weight Loss Efficacy
The mean change in bodyweight from baseline to week 44 was -16.0% (SE 0.7) for the semaglutide group versus -3.1% (0.9) for the placebo group (p < 0.0001). This represents a treatment difference of -12.9 percentage points. When looking at categorical weight loss, the results were equally striking:
- ≥5% weight loss: 96% (Sema) vs. 25% (Placebo)
- ≥10% weight loss: 78% (Sema) vs. 10% (Placebo)
- ≥15% weight loss: 53% (Sema) vs. 4.2% (Placebo)
Anthropometric and Metabolic Indicators
Beyond total body weight, the reduction in waist circumference was a major highlight. Participants in the semaglutide 2.4 mg group saw a mean reduction of 11.9 cm, compared to 3.0 cm in the placebo group (p < 0.0001). Given that visceral fat is a primary driver of cardiometabolic disease in Asians, this reduction suggests a substantial lowering of health risks.
Safety and Tolerability Profile
The safety profile of semaglutide 2.4 mg in this Asian population was consistent with findings from previous global STEP trials. Adverse events (AEs) were reported by 89% of the semaglutide group and 78% of the placebo group. The most common AEs were gastrointestinal in nature, including nausea, diarrhea, and vomiting, most of which were mild to moderate and transient. Serious adverse events occurred in 13% of the semaglutide group compared to 8% in the placebo group. Discontinuation due to adverse events was relatively low (6% in the treatment group).
Expert Commentary: Clinical and Policy Implications
The STEP 11 trial is a landmark study because it validates the use of high-dose GLP-1 receptor agonists in a population where the BMI threshold for obesity is lower. Many clinicians have historically been cautious about using dosages studied in Western populations (where BMIs are often >35 or >40) for Asian patients with BMIs in the 25-30 range. These findings provide the necessary confidence that the 2.4 mg dose is both highly effective and safe for this demographic.
From a public health and policy perspective, these results are transformative. By demonstrating such high efficacy at the BMI ≥25 threshold, the study provides a strong evidentiary basis for national health systems in South Korea and Thailand to include semaglutide 2.4 mg in their local treatment guidelines and, importantly, in reimbursement frameworks. Population-specific data is essential for justifying the cost-effectiveness of pharmacotherapy in obesity management.
Conclusion
The STEP 11 trial confirms that once-weekly semaglutide 2.4 mg, combined with lifestyle modifications, induces superior and clinically meaningful weight loss in Asian adults with a BMI of 25 kg/m2 or higher. The 16% weight reduction observed is comparable to results seen in broader global populations, suggesting that the drug’s mechanism of action is equally potent in Asian ethnicities. As obesity-related comorbidities continue to rise in Asia, STEP 11 offers a robust therapeutic pathway to mitigate these risks through early and effective intervention.
Funding and Trial Registration
The study was funded by Novo Nordisk. It is registered at ClinicalTrials.gov under the identifier NCT04998136.
References
Lim S, Buranapin S, Bao X, Quiroga M, Park KH, Kang JH, Rinnov AR, Suwanagool A. Once-weekly semaglutide 2·4 mg in an Asian population with obesity, defined as BMI ≥25 kg/m2, in South Korea and Thailand (STEP 11): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2025 Oct;13(10):838-847. doi: 10.1016/S2213-8587(25)00164-0. Epub 2025 Aug 15. PMID: 40825340.
