Background: Semaglutide 2·4 mg is a GLP-1 receptor agonist that reduces bodyweight, and provides other cardiometabolic benefits, among people with a BMI at least 30 kg/m2 or at least 27 kg/m2 and with weight-related comorbidities. This trial aimed to evaluate the efficacy, tolerability, and safety of semaglutide 2·4 mg in adults from mainland China and Taiwan with overweight or obesity according to locally defined, BMI thresholds.
Methods: This completed randomised, double-blind, placebo-controlled, multicentre, two-armed, parallel-group, phase 3b trial (STEP 12) was conducted at 19 sites across mainland China and Taiwan. Adults with a BMI of 24-<28 kg/m2 and at least one weight-related comorbidity, or a BMI of 28-<30 kg/m2, with or without type 2 diabetes, were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo, plus lifestyle intervention, for 44 weeks. Randomisation was performed by the study sponsor using the Randomisation Trial Supplies Management System. Coprimary endpoints were percentage change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction. Safety was analysed descriptively in all participants who received the trial intervention. Missing data at week 44 were imputed with washout multiple imputation. This study is registered with ClinicalTrials.gov, NCT06041217, and is completed.
Findings: Between Sept 15, 2023, and May 7, 2025, of 254 screened participants, 161 (66·5%) of 242 participants were randomly assigned to semaglutide 2·4 mg and 81 (33·5%) to placebo; 121 (50·0%) participants were female, and 47 (19·4%) participants had type 2 diabetes. Bodyweight reduction was greater with semaglutide versus placebo (-12·1% [SE 0·6] vs -2·2% [0·8]; estimated treatment difference -9·9 percentage points [95% CI -11·8 to -8·0]; p<0·0001), with a greater proportion of participants achieving at least 5% bodyweight reduction (80·5% vs 24·4%; odds ratio [OR] 14·8 [95% CI 7·4 to 29·6]; p<0·0001). Adverse events were reported in 141 (87·6%) of 161 participants in the semaglutide 2·4 mg group and 61 (75·3%) of 81 participants in the placebo group, with gastrointestinal disorders being the most common.
Interpretation: Semaglutide 2·4 mg provided a superior reduction in bodyweight versus placebo in Chinese adults with overweight or obesity. The safety profile was consistent with the known profile of semaglutide.
Funding: Novo Nordisk A/S.
Translation: For the Mandarin translation of the abstract see Supplementary Materials section.
This TimeCapsule reviews the major transformations in lipid metabolism and cardiovascular disease prevention during the first quarter of the 21st century and their impact on clinical practice. From late 20th century paradigms to current state-of-the-art strategies, the field has consolidated statins as foundational therapy while establishing the clinical benefit of non-statin agents and introducing biological therapies into cardiovascular disease prevention. These developments support the paradigm that lowering LDL-cholesterol levels earlier and sustaining this over time translates to greater reductions in cardiovascular risk. More recently, RNA-targeted and DNA-targeted approaches have enabled the modulation of proteins, such as PCSK9, lipoprotein(a), apolipoprotein C-III, and ANGPTL3. The traditional concept of HDL-cholesterol being considered a good cholesterol has been challenged, whereas the causal relevance of lipoprotein(a) has gained recognition. New metrics-including non-HDL-cholesterol, apolipoprotein B, triglyceride-rich remnants, or remnant cholesterol-are increasingly integrated into residual risk assessment. A growing sex-specific perspective has refined cardiovascular research and care. Despite robust evidence, the proportion of patients meeting their recommended targets remains unacceptably low. Implementation science seeks to address this persistent evidence-practice gap. In parallel, artificial intelligence is reshaping scientific methodologies and is poised to transform the understanding and management of lipid-related cardiometabolic disease.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：