胰岛素-naive 2 型糖尿病患者中使用带剂量指导应用程序的每周 1 次胰岛素 icodec 与每日 1 次基础胰岛素类似物的对比（ONWARDS 5）：一项随机试验。

Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5) : A Randomized Trial.

机构信息

LMC Diabetes and Endocrinology, Brampton, Ontario, Canada (H.S.B.).

University Medical Center Hamburg-Eppendorf, Hamburg, Germany (J.A.).

出版信息

Ann Intern Med. 2023 Nov;176(11):1476-1485. doi: 10.7326/M23-1288. Epub 2023 Sep 26.

DOI:10.7326/M23-1288

PMID:37748181

Abstract

BACKGROUND

Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden.

OBJECTIVE

To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice.

DESIGN

52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626).

SETTING

176 sites in 7 countries.

PARTICIPANTS

1085 insulin-naive adults with T2D.

INTERVENTION

Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300).

MEASUREMENTS

The primary outcome was change in glycated hemoglobin (HbA) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score).

RESULTS

The estimated mean change in HbA level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority ( < 0.001) and superiority ( = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], -0.38 percentage points [95% CI, -0.66 to -0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both treatments.

LIMITATION

Inability to differentiate the effects of icodec and the dosing guide app.

CONCLUSION

Compared with OD analogues, icodec with app showed superior HbA reduction and improved treatment satisfaction and compliance with similarly low hypoglycemia rates.

PRIMARY FUNDING SOURCE

Novo Nordisk A/S.

摘要

背景

对于 2 型糖尿病（T2D）患者，基础胰岛素剂量调整不足和用药依从性差可导致血糖控制不佳。icodec 是一种正在研发中的基础胰岛素类似物，每周注射一次，旨在减轻治疗负担。

目的

比较基于剂量调整指导应用程序（icodec 与 app）调整剂量的 icodec 与按照标准方案给药的每日一次基础胰岛素类似物（OD 类似物）的疗效和安全性。

设计

具有真实世界元素的 52 周、随机、开放标签、平行组、3a 期临床试验。（ClinicalTrials.gov：NCT04760626）。

地点

7 个国家的 176 个地点。

参与者

1085 名胰岛素初治的 T2D 成年患者。

干预措施

icodec 与 app 或 OD 类似物（地特胰岛素、甘精胰岛素 U100 或甘精胰岛素 U300）。

测量指标

主要结局指标是从基线到 52 周时糖化血红蛋白（HbA）水平的变化。次要结局指标包括患者报告的结局（糖尿病相关影响衡量工具 [TRIM-D] 依从性域评分和糖尿病治疗满意度问卷 [DTSQ] 总治疗满意度评分的变化）。

结果

与 OD 类似物相比，icodec 与 app 治疗使 HbA 水平从基线到 52 周的估计平均变化更大，且具有非劣效性（<0.001）和优效性（=0.009），符合预先设定的分层检验（估计治疗差异[ETD]，-0.38 个百分点[95%CI，-0.66 至-0.09 个百分点]）。在 52 周时，与 OD 类似物相比，患者报告的结局更有利于 icodec 与 app（ETD，TRIM-D 为 3.04[CI，1.28 至 4.81]，DTSQ 为 0.78[CI，0.10 至 1.47]）。两种治疗的严重或临床显著低血糖发生率均较低且相似。