The Cedar Centre, Royal Surrey Foundation Trust, Guildford, UK; Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
Lancet. 2023 Nov 4;402(10413):1636-1647. doi: 10.1016/S0140-6736(23)02179-7. Epub 2023 Oct 17.
ONWARDS 6 compared the efficacy and safety of once-weekly subcutaneous insulin icodec (icodec) and once-daily insulin degludec (degludec) in adults with type 1 diabetes.
This 52-week (26-week main phase plus a 26-week safety extension), randomised, open-label, treat-to-target, phase 3a trial was done at 99 sites across 12 countries. Adults with type 1 diabetes (glycated haemoglobin [HbA] <10·0% [86 mmol/mol]) were randomly assigned (1:1) to once-weekly icodec or once-daily degludec, both in combination with insulin aspart (two or more daily injections). The primary endpoint was change in HbA from baseline to week 26, tested for non-inferiority (0·3 percentage point margin) in all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04848480, and is now complete.
Between April 30 and Oct 15, 2021, of 655 participants screened, 582 participants were randomly assigned to icodec (n=290) or degludec (n=292). At week 26, from baseline values of 7·59% (icodec) and 7·63% (degludec), estimated mean changes in HbA were -0·47 percentage points and -0·51 percentage points, respectively (estimated treatment difference 0·05 percentage points [95% CI -0·13 to 0·23]), confirming non-inferiority of icodec to degludec (p=0·0065). Overall rate of combined clinically significant or severe hypoglycaemia (baseline to week 26) was statistically significantly higher with icodec than degludec (19·9 vs 10·4 events per patient-year of exposure; estimated rate ratio 1·9 [95% CI 1·5 to 2·3]; p<0·0001). The rate was also statistically significantly higher with icodec than degludec when evaluated over 57 weeks (52 weeks plus a 5-week follow-up period). 39 serious adverse events were reported in 24 (8%) participants receiving icodec, and 25 serious adverse events were reported in 20 (7%) participants receiving degludec. One participant in the icodec group died; this was judged unlikely to be due to the trial product.
In adults with type 1 diabetes, once-weekly icodec showed non-inferiority to once-daily degludec in HbA reduction at week 26, with statistically significantly higher rates of combined clinically significant or severe hypoglycaemia. For icodec, time below 3·0 mmol/L (<54 mg/dL) was at the threshold of the internationally recommended target (<1%) during weeks 22-26 and below target during weeks 48-52.
Novo Nordisk.
ONWARDS 6 比较了每周一次皮下注射胰岛素伊克德赛（icodec）和每日一次德古胰岛素（degludec）在 1 型糖尿病成人患者中的疗效和安全性。
这是一项为期 52 周（26 周主要阶段加 26 周安全性扩展）、随机、开放标签、以目标为导向、3a 期临床试验，在 12 个国家的 99 个地点进行。1 型糖尿病（糖化血红蛋白[HbA]<10.0%[86 mmol/mol]）的成年患者被随机分配（1:1）接受每周一次的伊克德赛或每日一次的德古胰岛素治疗，两者均与门冬胰岛素联合使用（每日两次或更多次注射）。主要终点是从基线到第 26 周时 HbA 的变化，在所有随机分配的参与者中测试非劣效性（0.3 个百分点的差值）。这项试验在 ClinicalTrials.gov 上注册，NCT04848480，现已完成。
在 2021 年 4 月 30 日至 10 月 15 日期间，在 655 名筛查的参与者中，有 582 名参与者被随机分配至伊克德赛组（n=290）或德古胰岛素组（n=292）。在第 26 周时，从基线值 7.59%（伊克德赛）和 7.63%（德古胰岛素），HbA 的估计平均变化分别为-0.47 个百分点和-0.51 个百分点，分别为（估计治疗差异 0.05 个百分点[95%CI-0.13 至 0.23]），证实伊克德赛在降低 HbA 方面不劣于德古胰岛素（p=0.0065）。与德古胰岛素相比，伊克德赛治疗组总的严重或临床显著低血糖事件（从基线到第 26 周）发生率具有统计学意义的升高（每患者年暴露事件发生率分别为 19.9 和 10.4；估计发生率比值 1.9[95%CI1.5 至 2.3]；p<0.0001）。当评估时间延长至 57 周（52 周加 5 周随访期）时，伊克德赛的发生率也具有统计学意义的升高。在接受伊克德赛治疗的 24 名（8%）参与者中报告了 39 例严重不良事件，在接受德古胰岛素治疗的 20 名（7%）参与者中报告了 25 例严重不良事件。伊克德赛组有 1 名参与者死亡；这被判断不太可能是由于试验产品导致的。
在 1 型糖尿病成人患者中，每周一次的伊克德赛在第 26 周时降低 HbA 方面不劣于每日一次的德古胰岛素，严重或临床显著低血糖的发生率具有统计学意义的升高。对于伊克德赛，在第 22-26 周时，血糖低于 3.0mmol/L（<54mg/dL）的时间接近国际推荐目标（<1%），在第 48-52 周时血糖低于目标。
诺和诺德。
