Alleviating carbohydrate counting in adults with type 1 diabetes with weekly Semaglutide injections added to an automated insulin delivery with Lyumjev

项目摘要/摘要 对1型糖尿病患者维持严格的血糖控制的主要挑战之一 (T1D)发生在用餐时间。目前对T1D患者的强化胰岛素治疗包括餐后胰岛素 丸剂取决于摄入的食物中的碳水化合物含量。然而，准确的 对于许多T1D患者来说，计算碳水化合物是一项具有挑战性和繁重的任务。在……里面 这项提议，我们的目标是简化用餐时间糖尿病的管理，将葡萄糖- 使用Lyumjev降低药物和我们的自动胰岛素输送(AID)系统。 胰升糖素样肽-1是一种由肠道内分泌细胞对葡萄糖作出反应而释放的激素 消费。外源性GLP-1受体激动剂(GLP-1RAs)已被开发为 通过(一)增加胰岛素分泌，(二)降低空腹和餐后血糖 胰高血糖素分泌，(Iii)减缓胃排空，以及(Iv)通过刺激饱腹感降低食欲 大脑中心。2型糖尿病的随机对照试验表明，GLP-1 RAS 在不增加低血糖的情况下改善血糖控制，最近关于1型糖尿病的数据 也显示了令人振奋的结果。Lyumjev是一种新的超快速胰岛素利斯普罗制剂，具有更快的 胰岛素的起效作用与常规胰岛素的利斯普罗比较。运送Lyumjev 在用餐时间显著降低餐后血糖水平并减少餐后增量 与Humalog相比，曲线下的面积。 我们的目标是进行2×2因子、随机、安慰剂对照、双盲、交叉试验 评估在Lyumjev的AID系统中加入赛马路德是否可以减轻负担 26名患有T1D的成年人，在不降低白天血糖控制的情况下，碳水化合物计数减少。这个 研究将由4个干预措施组成，每个干预措施为期4周，测试赛马路德加Lyumjev 具有(I)需要碳水化合物计数(辅助计数)的系统和(Ii)需要用餐的系统 仅公告(AID-公告)，以及安慰剂加Lyumjev(Iii)AID-Count和(Iv) 援助--宣布。药物序列的顺序(赛马路德与安慰剂)将是 随机1：1。在每个药物序列中，AID构型的顺序也将是 随机1：1。在每个药物序列开始时，将启动12周的剂量滴定周期。 在药物序列之间将应用2周的洗脱期。主要结果是 白天(6：00-24：00)在目标血糖范围(TIR)中花费的时间百分比，定义为 70-180 mg/dL，从SEMA加Lyumjev-AID宣布到安慰剂+4周- Lyumjev-AID-Count(控制臂)。我们假设SEMA加Lyumjev-AID将宣布 与控制臂相比，实现非劣质的日间TIR。 第1页，共1页

Project summary/Abstract One of the main challenges in maintaining tight glucose control in individuals with type 1 diabetes (T1D) occurs at mealtimes. Current intensive insulin therapy in T1D involves prandial insulin boluses dependent on the carbohydrate content of the ingested meal. However, accurate carbohydrate counting is a challenging and burdensome task for many individuals with T1D. In this proposal, we aim to simplify mealtime diabetes management with a combination of glucose- lowering drugs and our automated insulin delivery (AID) system using Lyumjev. Glucagon-Like-Peptide-1 is a hormone released by gut endocrine cells in response to glucose consumption. Exogenous GLP-1 receptor agonists (GLP-1 RAs) have been developed to decrease fasting and postprandial blood glucose by (i) increasing insulin secretion, (ii) decreasing glucagon secretion, (iii) slowing gastric emptying, and (iv) reducing appetite by stimulating satiety brain centers. Randomized controlled trials in type 2 diabetes have shown that GLP-1 RAs improve glucose control without increasing hypoglycemia, and recent data in type 1 diabetes have also shown promising results. Lyumjev is a novel ultra-rapid insulin lispro formulation with a faster onset of insulin action compared to the conventional insulin lispro – Humalog. Delivering Lyumjev at mealtimes significantly lowers postprandial glucose levels and reduces post-meal incremental area under the curve compared to Humalog. We aim to conduct a 2 × 2 factorial, randomized, placebo-controlled, double-blind, crossover trial to assess if the addition of Semaglutide to an AID system with Lyumjev can alleviate the burden of carbohydrate counting, without degrading daytime glucose control in 26 adults with T1D. The study will consist of 4 interventions, each 4-weeks in length, testing Semaglutide-plus-lyumjev with (i) a system that requires carb counting (AID-count) and (ii) a system that requires meal announcement only (AID-announce), as well as placebo-plus-lyumjev with (iii) AID-count and (iv) AID-announce. The order of the of the drug sequence (Semaglutide vs placebo) will be randomized 1:1. Within each drug sequence, the order of the AID configuration will also be randomized 1:1. At the start of each drug sequence, 12-week dose titration period will be initiated. A 2-week washout period will be applied between the drug sequences. The primary outcome is the daytime (6:00-24:00) percentage of time spent in the target glucose range (TIR), defined as 70-180mg/dL, over 4 weeks between sema-plus-lyumjev-AID-announce and placebo-plus- lyumjev-AID-count (control arm). We hypothesize that sema-plus-lyumjev-AID-announce will achieve non-inferior daytime TIR compared to the control arm. Page 1 of 1