丹麦哥本哈根大学Filip K Knop团队研究了每天服用一次索马鲁肽治疗非2型糖尿病成年人超重或肥胖的效果。2023年6月25日出版的《柳叶刀》杂志发表了这项成果。

研究组评估了每天服用一次胰高血糖素样肽-1类似物索马鲁肽50 mg与安慰剂治疗非2型糖尿病成年人超重或肥胖的疗效和安全性。

这项随机、双盲、安慰剂对照的3期优越性试验招募了BMI至少为30 kg/m²或至少为27 kg/m²的成年人，他们患有与体重相关的并发症和合并症，没有2型糖尿病。该试验在亚洲、欧洲和北美九个国家的50家门诊诊所进行。参与者通过互动网络反应系统随机分配（1:1）口服索马鲁肽至50 mg，或视觉匹配的安慰剂，每天一次，持续68周，外加生活方式干预。参与者、研究人员和评估结果的人均双盲。共同主要终点是体重的百分比变化，以及参与者在第68周口服50 mg索马鲁肽与安慰剂相比是否达到至少5%的体重减轻，无论是否停止治疗或使用其他降低体重的疗法（意向治疗分析）。对至少接受一剂试验药物的参与者进行了安全性评估。

2021年9月13日至11月22日，研究组对709名参与者进行了筛查，其中667人被随机分配至口服50 mg索马鲁肽（n=334）或安慰剂（n=333）。从基线到第68周，口服50 mg索马鲁肽的估计平均体重变化为-15.1%，而安慰剂为-24%（估计治疗差异为-12.7个百分点；p<0.0001）。第68周索马鲁肽组与安慰剂组比较，有更多的参与者体重至少减轻了5%（317人中有269人[85%] vs 295人中有76人[26%]；比值比[OR]为12.6；p＜0.0001）、10%（220人[69%] vs 35人[12%]；OR为14.7）、15%（170人[54%] vs 17人[6%]；OR为17.9）和20%（107人[34%] vs 8人[3%]；OR为18.5）。口服50 mg索马鲁肽（334例中有307例[92%]）的不良事件发生率高于安慰剂（333例中285例[86%]）。268名（80%）服用50 mg索马鲁肽的参与者和154名（46%）服用安慰剂的参与者报告了胃肠道不良事件（大多为轻度至中度）。

研究结果表明，在没有2型糖尿病的超重或肥胖成年人中，与安慰剂相比，每天口服一次50 mg的索马鲁肽可显著降低体重，并具有临床意义。

附：英文原文

Title: Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Filip K Knop, Vanita R Aroda, Ruben D do Vale, Thomas Holst-Hansen, Peter N Laursen, Julio Rosenstock, Domenica M Rubino, W Timothy Garvey

Issue&Volume: 2023-06-25

Abstract:

Background

We assessed the efficacy and safety of the oral glucagon-like peptide-1 analogue, semaglutide 50 mg, taken once per day versus placebo for the treatment of overweight or obesity in adults without type 2 diabetes.

Methods

This randomised, double-blind, placebo-controlled, phase 3, superiority trial enrolled adults with a BMI of at least 30 kg/m2, or at least 27 kg/m2 with bodyweight-related complications and comorbidities, without type 2 diabetes. The trial was done at 50 outpatient clinics in nine countries across Asia, Europe, and North America. Participants were randomly allocated (1:1) via an interactive web-response system to oral semaglutide escalated to 50 mg, or visually matching placebo, once per day for 68 weeks, plus lifestyle intervention. Group assignment was masked for participants, investigators, and those assessing outcomes. Coprimary endpoints were the percentage change in bodyweight and whether participants reached a bodyweight reduction of at least 5% at week 68 for oral semaglutide 50 mg versus placebo, assessed regardless of treatment discontinuation or use of other bodyweight-lowering therapies (an intention-to-treat analysis). Safety was assessed in participants who received at least one dose of trial drug. This trial, registered with ClinicalTrials.gov (NCT05035095), is now complete.

Findings

From Sept 13 to Nov 22, 2021, 709 participants were screened, of whom 667 were randomly assigned to oral semaglutide 50 mg (n=334) or placebo (n=333). The estimated mean bodyweight change from baseline to week 68 was –15·1% (SE 0·5) with oral semaglutide 50 mg versus –2·4% (0·5) with placebo (estimated treatment difference 12·7 percentage points, 95% CI 14·2 to 11·3; p<0·0001). More participants reached bodyweight reductions of at least 5% (269 [85%] of 317 vs 76 [26%] of 295; odds ratio [OR] 12·6, 95% CI 8·5 to 18·7; p<0·0001), 10% (220 [69%] vs 35 [12%]; OR 14·7, 9·6 to 22·6), 15% (170 [54%] vs 17 [6%]; OR 17·9, 10·4 to 30·7), and 20% (107 [34%] vs 8 [3%]; OR 18·5, 8·8 to 38·9) at week 68 with oral semaglutide 50 mg versus placebo. Adverse events were more frequent with oral semaglutide 50 mg (307 [92%] of 334) than with placebo (285 [86%] of 333). Gastrointestinal adverse events (mostly mild to moderate) were reported in 268 (80%) participants with oral semaglutide 50 mg and 154 (46%) with placebo.

Interpretation

In adults with overweight or obesity without type 2 diabetes, oral semaglutide 50 mg once per day led to a superior and clinically meaningful decrease in bodyweight compared with placebo.

DOI: 10.1016/S0140-6736(23)01185-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01185-6/fulltext