Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Diabetes Research Centre, University of Leicester, Leicester, UK.
Diabetes Obes Metab. 2023 Jan;25(1):18-35. doi: 10.1111/dom.14863. Epub 2022 Oct 18.
Obesity is a chronic, relapsing disease associated with multiple complications and a substantial morbidity, mortality and health care burden. Pharmacological treatments for obesity provide a valuable adjunct to lifestyle intervention, which often achieves only limited weight loss that is difficult to maintain. The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme is evaluating once-weekly subcutaneous semaglutide 2.4 mg (a glucagon-like peptide-1 analogue) in people with overweight or obesity. Across STEP 1, 3, 4 and 8, semaglutide 2.4 mg was associated with mean weight losses of 14.9%-17.4% in individuals with overweight or obesity without type 2 diabetes from baseline to week 68; 69%-79% of participants achieved ≥10% weight loss with semaglutide 2.4 mg (vs. 12%-27% with placebo) and 51%-64% achieved ≥15% weight loss (vs. 5%-13% with placebo). In STEP 5, mean weight loss was -15.2% with semaglutide 2.4 mg versus -2.6% with placebo from baseline to week 104. In STEP 2 (individuals with overweight or obesity, and type 2 diabetes), mean weight loss was -9.6% with semaglutide 2.4 mg versus -3.4% with placebo from baseline to week 68. Improvements in cardiometabolic risk factors, including high blood pressure, atherogenic lipids and benefits on physical function and quality of life were seen with semaglutide 2.4 mg. The safety profile of semaglutide 2.4 mg was consistent across trials, primarily gastrointestinal adverse events. The magnitude of weight loss reported in the STEP trials offers the potential for clinically relevant improvement for individuals with obesity-related diseases.
肥胖是一种与多种并发症相关的慢性、复发性疾病，给患者带来了巨大的发病和死亡风险，以及沉重的医疗负担。肥胖的药物治疗为生活方式干预提供了有价值的补充，而生活方式干预通常只能实现有限的减重，且难以维持。Semaglutide Treatment Effect in People with obesity（STEP）临床试验项目正在评估超重或肥胖人群每周一次皮下注射 2.4mg 司美格鲁肽（一种胰高血糖素样肽-1 类似物）的疗效。在 STEP 1、3、4 和 8 研究中，与安慰剂相比，司美格鲁肽 2.4mg 使基线至第 68 周时超重或肥胖且无 2 型糖尿病的个体平均体重分别降低 14.9%-17.4%；69%-79%的患者实现了≥10%的体重减轻（司美格鲁肽 2.4mg 组 vs. 安慰剂组 12%-27%），51%-64%的患者实现了≥15%的体重减轻（司美格鲁肽 2.4mg 组 vs. 安慰剂组 5%-13%）。在 STEP 5 研究中，与安慰剂相比，司美格鲁肽 2.4mg 使基线至第 104 周时的平均体重降低了-15.2%。在 STEP 2（超重或肥胖且患有 2 型糖尿病的患者）研究中，与安慰剂相比，司美格鲁肽 2.4mg 使基线至第 68 周时的平均体重降低了-9.6%。司美格鲁肽 2.4mg 还可改善心血管代谢风险因素，包括高血压、致动脉粥样硬化脂质，并有益于身体机能和生活质量。在各项研究中，司美格鲁肽 2.4mg 的安全性特征一致，主要为胃肠道不良事件。STEP 试验报告的减重幅度为肥胖相关疾病患者带来了具有临床意义的改善潜力。
