Semaglutide and Cardiovascular Outcomes in People with Type 2 Diabetes: A SUSTAIN-6 Post Hoc Analysis by Weight Loss Category.

IF 4.2 3区医学 Q2 Medicine

Diabetes Therapy Pub Date : 2026-06-01 Epub Date: 2026-05-09 DOI:10.1007/s13300-026-01875-3

Angelo Navas, Joshua Noone, Nathan Laney, Sunny Sheth, Xi Tan, Yuanjie Liang, Paloma Munoz, Caroline Swift

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引用次数: 0

Abstract

Introduction: Type 2 diabetes (T2D) is a known risk factor for cardiovascular (CV) disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, improve glycemic control and are associated with weight loss, but the impact of weight loss on major adverse cardiovascular events (MACE) when taking semaglutide is not fully understood. This post hoc analysis of the SUSTAIN-6 trial aimed to examine the correlation between weight loss with semaglutide and the occurrence of MACE (nonfatal myocardial infarction, nonfatal ischemic stroke, and CV death).

Methods: This study is a single-arm, post hoc, observational analysis of the randomized, double-blind, placebo-controlled SUSTAIN-6 cardiovascular outcomes trial (NCT01720446). Participants in the semaglutide group (N = 1479) were stratified into four weight loss categories on the basis of the percentage change in body weight from baseline to 56 weeks: no loss/gain, < 5% loss, 5-10% loss, and > 10% loss. The occurrence of MACE during the follow-up period (weeks 56-104) was compared across weight loss categories using descriptive statistics and logistic regression adjusted for age and sex. Categorical variables were compared across groups using chi-squared tests, and continuous variables were compared using analysis of variance (ANOVA).

Results: Point estimates of MACE incidence did not differ by weight loss category (P = 0.73). The MACE event rate was comparable across weight loss categories (no loss/gain: 1.05%; < 5% loss: 1.69%; loss 5-10%: 1.06%, > 10% loss: 0.89%). Compared with the no weight loss/gain category, no degree of weight loss was associated with lower adjusted odds (odds ratio) of MACE (loss < 5%: 1.68; P = 0.66; loss 5-10%: 1.13; P = 0.77; loss > 10%: 1.06; P = 0.95).

Conclusions: This post hoc analysis of SUSTAIN-6 did not find an association between the magnitude of weight loss achieved after 56 weeks of semaglutide treatment and subsequent MACE risk in people with T2D, suggesting that weight-independent mechanisms may mediate the cardioprotective effects of semaglutide.

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西马鲁肽和2型糖尿病患者的心血管结局：减重类别的持续-6事后分析

2型糖尿病（T2D）是已知的心血管（CV）疾病的危险因素。胰高血糖素样肽-1受体激动剂（GLP-1RAs），如西马鲁肽，可改善血糖控制并与体重减轻有关，但服用西马鲁肽时体重减轻对主要不良心血管事件（MACE）的影响尚不完全清楚。这项对SUSTAIN-6试验的事后分析旨在检验西马鲁肽减重与MACE（非致死性心肌梗死、非致死性缺血性卒中和CV死亡）发生之间的相关性。方法：本研究是一项随机、双盲、安慰剂对照的SUSTAIN-6心血管结局试验（NCT01720446）的单臂、事后观察分析。semaglutide组的参与者（N = 1479）根据体重从基线到56周的百分比变化分为四个减肥类别：无减重/增重，减重10%。在随访期间（第56-104周），使用描述性统计和经年龄和性别调整的逻辑回归对不同减肥类别的MACE发生率进行比较。分类变量采用卡方检验进行组间比较，连续变量采用方差分析（ANOVA）进行比较。结果：MACE发生率的点估计值没有因减肥类别而异（P = 0.73）。不同减肥类别的MACE事件发生率具有可比性（无减重/增重：1.05%；减重10%:0.89%）。与无增重/减重组相比，无减重程度组的MACE调整比值（比值比）较低（减重10%:1.06;P = 0.95）。结论：这项对SUSTAIN-6的事后分析没有发现在56周的西马鲁肽治疗后体重减轻的程度与T2D患者随后的MACE风险之间存在关联，这表明体重无关的机制可能介导了西马鲁肽的心脏保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes Therapy Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

6.90

自引率

7.90%

发文量

130

审稿时长

6 weeks

期刊介绍： Diabetes Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all areas of diabetes. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Diabetes Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.