Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes - (ARMMS-T2D)

摘要 减肥/代谢手术治疗2型糖尿病初期缓解的短期安全性和有效性 (T2D)在中度至重度肥胖患者中的应用已得到充分证实。然而，没有前景 随机对照试验（RCT）测试了这种方法的长期有效性、持久性和安全性。 此外，关于肥胖/代谢手术在以下患者中的风险和获益的1级证据 糖尿病和仅轻度肥胖是有限的。在这方面，四个调查小组（克利夫兰诊所，乔斯林 糖尿病中心/波士顿布里格姆妇女医院、匹兹堡大学和 华盛顿）已经完成了随机对照试验，评价了 肥胖/代谢手术与T2 D和身体的多学科医学和生活方式管理的比较 体重，包括仅轻度肥胖或仅超重的患者。调查人员从这些 四项随机对照试验现已组成2型糖尿病药物与代谢手术随机试验联盟， 糖尿病（ARMMS-T2 D）联盟。在NIH U34计划拨款的支持下，我们准备了这个 U 01应用程序，以获得302例BMI为27-45 kg/m2（35%）的T2 D患者的长期随访数据 基线BMI <35 kg/m2），随机接受手术或非手术糖尿病管理 接近。这些随机对照试验包括一套通用的测量方法，所有这些试验均已完成并发表 至少一年的后续评估。通过U34机制，我们合并了研究参与者， 将研究程序和结局指标统一为统一的、前瞻性的、纵向的、观察性的 到目前为止，我们已经成功地招募了244名参与者进入短期2年随访。的 本U 01的主要目标是确定血糖控制的长期（7年）持久性（ HbA 1c相对于基线）。 次要结局包括糖尿病缓解率和复发率，疗效结局包括禁食 血糖、体重、血脂、血压、白蛋白尿、大血管和微血管事件， 心脏代谢风险评分、生活质量和安全性，包括低血糖和主要心血管疾病 事件在探索性分析中，我们将确定糖尿病缓解和复发的临床预测因素。我们 一个大型的、统一的队列将形成第一个解决这些问题的RCT，它代表了一种具有成本效益的方法， 产生重要的长期数据。ARMMS-T2 D预计将产生很大的影响，因为它将提供 最大规模的长期1级证据，可为有关比较耐久性的决策提供信息， 肥胖/代谢手术相对于T2 D药物/生活方式管理的有效性和安全性， 轻度至中度肥胖患者。

ABSTRACT The short-term safety and efficacy of bariatric/metabolic surgery for the initial remission of type 2 diabetes (T2D) in patients with moderate to severe obesity is well established. However, there are no prospective randomized controlled trials (RCTs) that have tested long-term efficacy, durability, and safety of this approach. Moreover, Level-1 evidence regarding the risks and benefits of bariatric/metabolic surgery in patients with diabetes and only mild obesity is limited. In this context, four investigative groups (Cleveland Clinic, Joslin Diabetes Center/Brigham & Women's Hospital Boston, the University of Pittsburgh, and the University of Washington) have completed RCTs that evaluated the short-term (1-3 years) effectiveness of bariatric/metabolic surgery compared to multidisciplinary medical and lifestyle management of T2D and body weight, including among patients who are only mildly obese or merely overweight. Investigators from these four RCTs have now formed the Alliance of Randomized Trials of Medicine versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) consortium. With the support of an NIH U34 planning grant, we have prepared this U01 application to obtain long-term follow-up data from 302 patients with T2D and a BMI of 27-45 kg/m2 (35% with baseline BMI <35 kg/m2), who were randomized to surgical or non-surgical diabetes management approaches. These RCTs include a set of common measures, and all of them have completed and published at least one-year follow-up assessments. Through the U34 mechanism, we merged study participants and harmonized study procedures and outcome metrics into a unified, prospective, longitudinal, observational framework, and to date, we have successfully enrolled 244 participants into a short-term 2 year follow-up. The primary goal of this U01 is to determine long-term (7-year) durability of glycemic control (percentage change in HbA1c from baseline) following random treatment allocation to bariatric surgery or medical/lifestyle intervention. Secondary outcomes include rates of diabetes remission and relapse, efficacy outcomes including fasting plasma glucose, body weight, blood lipids, blood pressure, albuminuria, macro- and microvascular events, cardiometabolic risk score, and quality of life, and safety including hypoglycemia and major cardiovascular events. In exploratory analyses, we will identify clinical predictors of diabetes remission and relapse. Our large, unified cohort will form the first RCT to address these questions, and it represents a cost-effective way to generate essential long-term data. ARMMS-T2D is expected to have high impact because it will provide the largest body of long-term Level-1 evidence to inform decision-making regarding comparative durability, efficacy, and safety of bariatric/metabolic surgery relative to medical/lifestyle management of T2D among patients with mild to moderate obesity.