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)在中到重度肥胖症患者中得到了很好的证实。然而，没有预期的 已经测试了这种方法的长期有效性、持久性和安全性的随机对照试验(RCT)。 此外，关于减肥/代谢性手术的风险和益处的一级证据表明， 糖尿病和只有轻度肥胖是有限的。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大学 华盛顿)已经完成了评估短期(1-3年)有效性的随机对照试验 减肥/代谢外科与T2D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仅超重的患者。来自这些国家的调查人员 四个随机对照试验现在组成了2型药物与代谢外科随机试验的联盟 糖尿病(ARMMS-T2D)联盟。在NIH U34规划拨款的支持下，我们准备了这个 U01应用程序获得302名T2D患者的长期随访数据，BMI为27-45 kg/m2(35% 基线体重指数和35公斤/平方米)，他们被随机分为手术或非手术糖尿病治疗组 接近了。这些区域协调机制包括一套共同的措施，所有这些措施都已完成并公布 至少一年的跟踪评估。通过U34机制，我们将研究参与者和 将研究程序和结果指标统一为统一的、前瞻性的、纵向的、观察性的 框架，到目前为止，我们已经成功地招募了244名参与者参加为期两年的短期随访。这个 本U01的主要目标是确定血糖控制的长期(7年)持久性( HbA1c从基线开始)，随后随机分配治疗到减肥手术或医疗/生活方式干预。 次要结果包括糖尿病缓解率和复发率，疗效结果包括禁食 血糖，体重，血脂，血压，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。我们的 大型的统一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式 生成重要的长期数据。ARMMS-T2D预计将产生很大影响，因为它将提供 最大的长期一级证据，为关于相对耐久性的决策提供信息， 与T2D的医疗/生活方式管理相关的减肥/代谢手术的有效性和安全性 轻至中度肥胖的患者。

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.