美国德克萨斯大学西南医学中心Ildiko Lingvay团队研究了超重或肥胖和2型糖尿病的成人每周使用2.4 mg索马鲁肽的减重效果。2021年3月2日，该研究发表在《柳叶刀》杂志上。
本试验评估了GLP-1类似物每周皮下注射2.4 mg索马鲁肽与1.0 mg索马鲁肽（糖尿病治疗的批准剂量）和安慰剂对超重或肥胖以及2型糖尿病成人体重管理的疗效和安全性。
在这项双盲、双模拟、临床3期、优势研究中，研究组从欧洲、北美、南美、中东、南非和亚洲12个国家的149家门诊中招募体重指数至少为27 kg/m2、糖化血红蛋白7–10%的成年人，他们在筛查前至少180天确诊为2型糖尿病。将其按1：1：1的比例随机分组，分别每周皮下注射2.4 mg索马鲁肽、1.0 mg索马鲁肽、或视觉匹配安慰剂，共68周，外加生活方式干预。主要终点是体重的百分比变化和在68周时体重减轻至少5%的患者比率。
2018年6月4日至11月14日，研究组共筛选了1595名患者，其中1210名患者被随机分组，索马鲁肽2.4 mg组中404例，索马鲁肽1.0 mg组中403例，安慰剂组中403，并纳入意向治疗分析。索马鲁肽2.4 mg组的平均体重从基线到68周估计下降了9.6%，安慰剂组估计下降了3.4%，两组相差6.2个百分点，差异显著。
在第68周，索马鲁肽2.4 mg组中有68.8%的患者体重减轻5%以上，显著高于安慰剂组（28.5%），比值比为4.88。索马鲁肽2.4 mg组中的不良事件发生率为87.6%，索马鲁肽1.0 mg组为81.8%，均高于安慰剂组（76.9%）。其中索马鲁肽2.4 mg组中有63.5%的患者出现胃肠道不良事件，索马鲁肽1.0 mg组中有57.5%，安慰剂组中有34.3%。
研究结果表明，对于超重或肥胖以及2型糖尿病的成人，与安慰剂相比，每周接受2.4 mg的索马鲁肽可显著降低体重。
附：英文原文
Title: Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial
Author: Melanie Davies, Louise Frch, Ole K Jeppesen, Arash Pakseresht, Sue D Pedersen, Leigh Perreault, Julio Rosenstock, Iichiro Shimomura, Adie Viljoen, Thomas A Wadden, Ildiko Lingvay
Issue&Volume: 2021-03-02
Abstract:
Background
This trial assessed the efficacy and safety of the GLP-1 analogue once a week subcutaneous semaglutide 2·4 mg versus semaglutide 1·0 mg (the dose approved for diabetes treatment) and placebo for weight management in adults with overweight or obesity, and type 2 diabetes.
Methods
This double-blind, double-dummy, phase 3, superiority study enrolled adults with a body-mass index of at least 27 kg/m 2 and glycated haemoglobin 7–10% (53–86 mmol/mol) who had been diagnosed with type 2 diabetes at least 180 days before screening. Patients were recruited from 149 outpatient clinics in 12 countries across Europe, North America, South America, the Middle East, South Africa, and Asia. Patients were randomly allocated (1:1:1) via an interactive web-response system and stratified by background glucose-lowering medication and glycated haemoglobin, to subcutaneous injection of semaglutide 2·4 mg, or semaglutide 1·0 mg, or visually matching placebo, once a week for 68 weeks, plus a lifestyle intervention. Patients, investigators, and those assessing outcomes were masked to group assignment. Coprimary endpoints were percentage change in bodyweight and achievement of weight reduction of at least 5% at 68 weeks for semaglutide 2·4 mg versus placebo, assessed by intention to treat. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03552757 and is closed to new participants.
Findings
From June 4 to Nov 14, 2018, 1595 patients were screened, of whom 1210 were randomly assigned to semaglutide 2·4 mg (n=404), semaglutide 1·0 mg (n=403), or placebo (n=403) and included in the intention-to-treat analysis. Estimated change in mean bodyweight from baseline to week 68 was 9·6% (SE 0·4) with semaglutide 2·4 mg vs 3·4% (0·4) with placebo. Estimated treatment difference for semaglutide 2·4 mg versus placebo was 6·2 percentage points (95% CI 7·3 to 5·2; p<0·0001). At week 68, more patients on semaglutide 2·4 mg than on placebo achieved weight reductions of at least 5% (267 [68·8%] of 388 vs 107 [28·5%] of 376; odds ratio 4·88, 95% CI 3·58 to 6·64; p<0·0001). Adverse events were more frequent with semaglutide 2·4 mg (in 353 [87·6%] of 403 patients) and 1·0 mg (329 [81·8%] of 402) than with placebo (309 [76·9%] of 402). Gastrointestinal adverse events, which were mostly mild to moderate, were reported in 256 (63·5%) of 403 patients with semaglutide 2·4 mg, 231 (57·5%) of 402 with semaglutide 1·0 mg, and 138 (34·3%) of 402 with placebo.
Interpretation
In adults with overweight or obesity, and type 2 diabetes, semaglutide 2·4 mg once a week achieved a superior and clinically meaningful decrease in bodyweight compared with placebo.
DOI: 10.1016/S0140-6736(21)00213-0
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00213-0/fulltext
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