Pragmatic Clinical Trial of Continuous Glucose Monitoring-based Interventions for Safe Insulin Prescribing in High-Risk Older Patients with Type 2 Diabetes

摘要 低血糖是2型糖尿病(T2D)胰岛素治疗的常见和可预防的并发症 随着年龄的增长，这一比例会急剧增加。在老年人(≥75岁)中，低血糖占所有患者的20% 急诊科因药物不良事件(主要是由于胰岛素)入院。降血糖 老年人的发病也与跌倒相关骨折的发生率增加有关， 心血管事件、认知功能下降和痴呆症、住院、自我报告质量较差 生命和死亡。对于需要胰岛素的T2D患者，最佳剂量需要监测血糖 在胰岛素类型和剂量、饮食、体力活动、健康状况、 和症状。当胰岛素方案不匹配时，任何时候都可能发生严重的低血糖 相应的患者需求。在老年患者中，经常自我监测血糖(SMBG) 使用传统的指纹支票通常在物理上是不可能的(也不是可取的)。此外，许多人 长期T2D的老年患者没有意识到低血糖(这是严重 低血糖)和/或对低血糖的恐惧(相应地不愿注射全部剂量的胰岛素)。 R01研究提案的首要目标是支持对需要胰岛素的更安全的管理， 患有T2D的老年人(年龄≥，75岁)有严重低血糖的高风险。我们将测试假设，在 这些患有T2D的高危老年人，这是一个基于团体的教育计划，纳入了Alarm- 启用持续血糖监测(CGM)将减少严重低血糖的发生率，因为 被美国糖尿病协会定义为需要另一个人的积极帮助来 实施复苏措施。目标1：我们将进行三组随机、务实的临床试验 旨在测试两种干预策略的效果，ARM 1-患者专用和ARM 2-患者+ 药剂师与ARM 3-大型综合护理提供系统中的常规护理(Kaiser 永久北加州)。这种三臂设计使我们能够检查两个版本的 基于CGM的方案实施需要不同水平的卫生系统投资(即， 在增加或不增加临床人员的情况下进行患者教育和培训)。目标2：我们还将检查 临床情况下干预治疗效果的异质性(基线血糖控制，并发 合并症)和患者情况(年龄、健康素养)，为今后的适应和传播提供信息 战略。这一安全导向的干预策略结合了启用警报的CGM，可提供 帮助高危患者降低重症心脏病发病率的低负担方法的潜力 低血糖症。如果成功，这项研究中的随机对照试验证据将支持新的护理模式 旨在改善T2D老年人的患者安全性和以患者为中心的预后。

Abstract Hypoglycemia is a common and preventable complication of insulin treatment in type 2 diabetes (T2D) that increases dramatically with age. In older adults (age ≥ 75), hypoglycemia accounts for 20% of all Emergency Department admissions for adverse drug events (primarily due to insulin). Hypoglycemic episodes in older adults are also associated with increased incidence of fall-related fractures, cardiovascular events, cognitive decline and dementia, hospitalization, worse self-reported quality of life, and mortality. For patients with T2D requiring insulin, optimal dosing requires monitoring glucose levels and directional trends in the context of insulin type and dose, diet, physical activity, health status, and symptoms. Severe hypoglycemia can occur at any time when the insulin regimen does not match the corresponding patient needs. In older patients, frequent self-monitoring of blood glucose (SMBG) using traditional fingerstick checks are often not physically possible (nor desirable). Moreover, many older patients with long duration T2D have hypoglycemia unawareness (a potent risk factor for severe hypoglycemia) and/or fear of hypoglycemia (with corresponding reluctance to inject full insulin dose). The overarching goal of this R01 research proposal is to support safer management of insulin-requiring, older adults (age ≥ 75) with T2D at high risk of severe hypoglycemia. We will test the hypothesis that in these high-risk older adults with T2D, a group-based educational program that incorporates alarm- enabled continuous glucose monitoring (CGM) will reduce the incidence of severe hypoglycemia as defined by the American Diabetes Association as requiring active assistance from another person to administer resuscitative measures. AIM 1: We will conduct a 3-arm randomized, pragmatic clinical trial designed to test the efficacy of two intervention strategies, Arm 1 – Patient-only and Arm 2 - Patient + Pharmacist compared to Arm 3 – Usual Care within a large, integrated care delivery system (Kaiser Permanente Northern California). This 3-arm design allows us to examine the impact of two versions of CGM-based program implementation that require different levels of health system investment (i.e., patient-education and training with or without added clinical personnel). AIM 2: We will also examine heterogeneity of intervention treatment effects by clinical context (baseline glycemic control, concurrent comorbidity) and patient context (age, health literacy) to inform future adaptation and dissemination strategies. This safety-oriented intervention strategy incorporating alarm-enabled CGM provides the potential for a low-burden approach to helping high-risk patients reduce incidence of severe hypoglycemia. If successful, the RCT evidence from this study will support new models of care designed to improve patient safety and patient-centered outcomes for older adults with T2D.