每周一次司美格鲁肽治疗肥胖合并膝关节骨关节炎患者的疗效

Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.

机构信息

From the Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen (H. Bliddal, L.E.K.), and Novo Nordisk, Søborg (T.H.M., A.K., J.S.N., A.W.) - both in Denmark; Louisville Metabolic and Atherosclerosis Research Center, University of Louisville School of Medicine, Louisville, KY (H. Bays); the Department of Nutrition, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris (S.C.); the Obesity Department, Capio St. Göran's Hospital, and Medical Department at the Karolinska Institute, Stockholm (J.U.H.); the Department of Endocrinology, Obesity, and Nutrition, Vestfold Hospital Trust, Tønsberg, and the Department of Endocrinology, Morbid Obesity, and Preventive Medicine, Institute of Clinical Medicine, University of Oslo, Oslo - both in Norway (J.H.); Centro de Investigación en Reumatología y Especialidades Médicas, Bogota, Colombia (P.V.S.); and the University of Toronto and York University, Toronto, McMaster University, Hamilton, ON, and Wharton Medical Clinic Weight and Diabetes Management, Burlington, ON - all in Canada (S.W.).

出版信息

N Engl J Med. 2024 Oct 31;391(17):1573-1583. doi: 10.1056/NEJMoa2403664.

DOI:10.1056/NEJMoa2403664

PMID:39476339

Abstract

BACKGROUND

Weight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied.

METHODS

We conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries. Participants with obesity (a body-mass index [BMI; the weight in kilograms divided by the square of the height in meters] of ≥30) and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain were randomly assigned, in a 2:1 ratio, to receive once-weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counseling on physical activity and a reduced-calorie diet. The primary end points were the percentage change in body weight and the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (on a scale of 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. A key confirmatory secondary end point was the physical-function score on the 36-Item Short Form Health Survey (SF-36), version 2 (on a scale of 0 to 100, with higher scores indicating greater well-being).

RESULTS

A total of 407 participants were enrolled. The mean age was 56 years, the mean BMI 40.3, and the mean WOMAC pain score 70.9. A total of 81.6% of the participants were women. The mean change in body weight from baseline to week 68 was -13.7% with semaglutide and -3.2% with placebo (P<0.001). The mean change in the WOMAC pain score at week 68 was -41.7 points with semaglutide and -27.5 points with placebo (P<0.001). Participants in the semaglutide group had a greater improvement in SF-36 physical-function score than those in the placebo group (mean change, 12.0 points vs. 6.5 points; P<0.001). The incidence of serious adverse events was similar in the two groups. Adverse events that led to permanent discontinuation of the trial regimen occurred in 6.7% of the participants in the semaglutide group and in 3.0% in the placebo group, with gastrointestinal disorders being the most common reason for discontinuation.

CONCLUSIONS

Among participants with obesity and knee osteoarthritis with moderate-to-severe pain, treatment with once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis than placebo. (Funded by Novo Nordisk; STEP 9 ClinicalTrials.gov number, NCT05064735.).

摘要

背景

减重已被证明可缓解膝骨关节炎的症状，包括疼痛。胰高血糖素样肽-1 受体激动剂对肥胖人群膝骨关节炎结局的影响尚未得到很好的研究。

方法

我们在 11 个国家的 61 个地点进行了一项为期 68 周、双盲、随机、安慰剂对照试验。参与者为肥胖者（体重指数[BMI；体重以千克为单位除以身高以米为单位的平方]≥30）和有临床和放射学诊断的中度膝关节骨关节炎，疼痛至少为中度，并随机分配，按 2:1 的比例接受每周一次皮下注射司美格鲁肽（2.4 毫克）或安慰剂，同时接受身体活动和低热量饮食咨询。主要终点是从基线到第 68 周时体重的百分比变化和西部安大略省和麦克马斯特大学骨关节炎指数（WOMAC）疼痛评分的变化（范围为 0 到 100，分数越高表示结果越差）。一个关键的确认性次要终点是 36 项简短健康调查（SF-36）版本 2 的身体功能评分（范围为 0 到 100，分数越高表示幸福感越高）。

结果

共纳入 407 名参与者。平均年龄为 56 岁，平均 BMI 为 40.3，平均 WOMAC 疼痛评分为 70.9。参与者中 81.6%为女性。从基线到第 68 周时，司美格鲁肽组的体重平均变化为-13.7%，安慰剂组为-3.2%（P<0.001）。第 68 周时，司美格鲁肽组 WOMAC 疼痛评分的平均变化为-41.7 分，安慰剂组为-27.5 分（P<0.001）。与安慰剂组相比，司美格鲁肽组的 SF-36 身体功能评分改善更大（平均变化，12.0 分 vs. 6.5 分；P<0.001）。两组严重不良事件的发生率相似。司美格鲁肽组有 6.7%的参与者因不良事件而永久停止试验方案，安慰剂组有 3.0%，最常见的停药原因为胃肠道疾病。