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

通过每周注射索马鲁肽并添加 Lyumjev 自动胰岛素输送来减少 1 型糖尿病成人患者的碳水化合物计数

• 批准号: 10636689
• 负责人: Michael Tsoukas
• 金额: $ 15万
• 依托单位: MCGILL UNIVERSITY HEALTH CTR RES INST
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10636689
• 关键词: Adherence; Adult; Agonist; Area Under Curve; Beta Cell; Blood Glucose; Body Weight decreased; Bolus Infusion; Brain; C-Peptide; Carbohydrates; Cell physiology; Clinical; Clinical Trials; Consumption; Cross-Over Trials; Data; Devices; Distress; Dose; Double-Blind Method; Emotional; Fasting; Formulation; Future; GLP-I receptor; Gastric Emptying; Glucagon; Glucose; Glycosylated hemoglobin A; Goals; Hormones; Hypoglycemia; Individual; Ingestion; Injections; Insulin; Insulin, Lispro, Human; Insulin-Dependent Diabetes Mellitus; Intervention; Label; Lead; Length; Measures; Non-Insulin-Dependent Diabetes Mellitus; Patients; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Placebo Control; Placebos; Population; Quality of life; Randomized; Randomized, Controlled Trials; Reporting; Satiation; Surveys; System; Testing; Time; Titrations; analog; arm; blood glucose regulation; comparison control; design; diabetes distress; diabetes management; diabetes self-management; glucagon-like peptide 1; glycemic control; gut endocrine cell; improved; increased appetite; insulin secretion; interest; novel; novel strategies; primary outcome; response; trial comparing

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

项目概要/摘要 1型糖尿病患者维持严格血糖控制的主要挑战之一 (T1D)发生在吃饭的时候。目前T1 D的强化胰岛素治疗涉及餐时胰岛素 大剂量取决于摄入膳食的碳水化合物含量。然而，准确 对于许多患有T1 D的个体来说，碳水化合物计数是一项具有挑战性和繁重的任务。在 这项建议，我们的目标是简化餐时糖尿病管理与葡萄糖的组合， 降低药物和我们的自动胰岛素输送系统（AID）使用Lyumjev。 胰高血糖素样肽-1是由肠道内分泌细胞响应葡萄糖而释放的激素 消费已经开发了外源性GLP-1受体激动剂（GLP-1 RA）， 通过（i）增加胰岛素分泌，（ii）降低空腹和餐后血糖， 胰高血糖素分泌，（iii）减缓胃排空，和（iv）通过刺激饱腹感降低食欲 大脑中枢2型糖尿病的随机对照试验表明，GLP-1 RA 改善葡萄糖控制而不增加低血糖，最近1型糖尿病的数据表明， 也取得了可喜的成果。Lyumjev是一种新型超速效赖脯胰岛素制剂， 与传统赖脯胰岛素-优泌乐相比，胰岛素作用的开始。交付柳姆耶夫 显著降低餐后血糖水平， 曲线下面积与Humanoid相比。 我们的目的是进行一项2 × 2析因、随机、安慰剂对照、双盲、交叉试验 以评估是否将Semaldehyde添加到Lyumjev的AID系统中可以减轻负担 碳水化合物计数，而不会降低26名T1 D成人的日间血糖控制。的 研究将包括4项干预措施，每项干预措施持续4周，检测Semaglutide + lyumjev （i）需要碳水化合物计数（AID计数）的系统和（ii）需要膳食的系统 仅公告（AID-announce），以及安慰剂加lyumjev与（iii）艾滋病计数和（iv） AID-announce.药物顺序（Semtetransomers vs安慰剂）的顺序为 随机1：1。在每个药物序列内，AID配置的顺序也将是 随机1：1。在每个药物序列开始时，将启动12周剂量滴定期。 在药物序列之间将应用2周洗脱期。主要结局是 白天（6：00-24：00）处于目标血糖范围（TIR）的时间百分比，定义为 70- 180 mg/dL，在sema + lyumjev-AID-announce和安慰剂+ lyumjev-AID-count（对照组）。我们假设sema-plus-lyumjev-AID-announce将 与对照组相比，实现非劣效的日间TIR。 页1的1