Bonaca Marc P, Catarig Andrei-Mircea, Houlind Kim, Ludvik Bernhard, Nordanstig Joakim, Ramesh Chethana Kalmady, Rasouli Neda, Sourij Harald, Videmark Alex, Verma Subodh
CPC Clinical Research, Cardiovascular Division, University of Colorado School of Medicine, Aurora, CO, USA.
Novo Nordisk, Søborg, Denmark.
Lancet. 2025 May 3;405(10489):1580-1593. doi: 10.1016/S0140-6736(25)00509-4. Epub 2025 Mar 29.
Peripheral artery disease is a highly morbid type of atherosclerotic vascular disease involving the legs and is estimated to affect over 230 million individuals globally. Few therapies improve functional capacity and health-related quality of life in people with lower limb peripheral artery disease. We aimed to evaluate whether semaglutide improves function as measured by walking ability as well as symptoms, quality of life, and outcomes in people with peripheral artery disease and type 2 diabetes.
STRIDE was a double-blind, randomised, placebo-controlled trial done at 112 outpatient clinical trial sites in 20 countries in North America, Asia, and Europe. Participants were aged 18 years and older, with type 2 diabetes and peripheral artery disease with intermittent claudication (Fontaine stage IIa, able to walk >200 m) and an ankle-brachial index of less than or equal to 0·90 or toe-brachial index of less than or equal to 0·70. Participants were randomly assigned (1:1) using an interactive web response system to receive subcutaneous semaglutide 1·0 mg once per week for 52 weeks or placebo. The primary endpoint was the ratio to baseline of the maximum walking distance at week 52 measured on a constant load treadmill in the full analysis set. Safety was evaluated in the safety analysis set. This trial is registered with ClinicalTrials.gov, NCT04560998 and is now completed.
From Oct 1, 2020, to July 12, 2024, 1363 patients were screened for eligibility, of whom 792 were randomly assigned to semaglutide (n=396) or placebo (n=396). 195 (25%) participants were female and 597 (75%) were male. Median age was 68·0 years (IQR 61·0-73·0). The estimated median ratio to baseline in maximum walking distance at week 52 was significantly greater in the semaglutide group than the placebo group (1·21 [IQR 0·95-1·55] vs 1·08 [0·86-1·36]; estimated treatment ratio 1·13 [95% CI 1·06-1·21]; p=0·0004). Six serious adverse events in five (1%) participants in the semaglutide group and nine serious adverse events in six (2%) participants in the placebo group were possibly or probably treatment related, with the most frequent being serious gastrointestinal events (two events reports by two [1%] in the semaglutide group and five events reported by three [1%] in the placebo group). There were no treatment-related deaths.
Semaglutide increased walking distance in patients with symptomatic peripheral artery disease and type 2 diabetes. Research implications include the need for future studies to further elucidate mechanisms of benefit and to assess the efficacy and safety in patients with peripheral artery disease who do not have type 2 diabetes.
Novo Nordisk.
外周动脉疾病是一种累及下肢的高发性动脉粥样硬化性血管疾病，据估计全球有超过2.3亿人受其影响。很少有疗法能改善下肢外周动脉疾病患者的功能能力和与健康相关的生活质量。我们旨在评估司美格鲁肽是否能改善外周动脉疾病合并2型糖尿病患者的步行能力、症状、生活质量和预后。
STRIDE是一项双盲、随机、安慰剂对照试验，在北美、亚洲和欧洲20个国家的112个门诊临床试验点进行。参与者年龄在18岁及以上，患有2型糖尿病和伴有间歇性跛行的外周动脉疾病（Fontaine IIa期，能够行走超过200米），踝臂指数小于或等于0.90或趾臂指数小于或等于0.70。参与者使用交互式网络响应系统随机分配（1:1），接受皮下注射司美格鲁肽1.0毫克，每周一次，共52周，或安慰剂。主要终点是在全分析集中，第52周在恒定负荷跑步机上测量的最大步行距离与基线的比值。在安全性分析集中评估安全性。该试验已在ClinicalTrials.gov注册，NCT04560998，现已完成。
从2020年10月1日至2024年7月12日，1363名患者接受了资格筛查，其中792名被随机分配至司美格鲁肽组（n = 396）或安慰剂组（n = 396）。195名（25%）参与者为女性，597名（75%）为男性。中位年龄为68.0岁（IQR 61.0 - 73.0）。司美格鲁肽组第52周最大步行距离相对于基线的估计中位比值显著高于安慰剂组（1.21 [IQR 0.95 - 1.55] 对比 1.08 [0.86 - 1.36]；估计治疗比值1.13 [95% CI 1.06 - 1.21]；p = 0.0004）。司美格鲁肽组5名（1%）参与者发生6起严重不良事件，安慰剂组6名（2%）参与者发生9起严重不良事件，可能或很可能与治疗相关，最常见的是严重胃肠道事件（司美格鲁肽组2名 [1%] 报告2起事件，安慰剂组3名 [1%] 报告5起事件）。没有与治疗相关的死亡。
司美格鲁肽增加了有症状外周动脉疾病合并2型糖尿病患者的步行距离。研究意义包括未来需要进一步阐明获益机制，并评估在无2型糖尿病的外周动脉疾病患者中的疗效和安全性。
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