每周一次胰岛素 efSitara 阿尔法与每日一次胰岛素德谷胰岛素在 1 型糖尿病成人患者中的比较（QWINT-5）：一项 3 期随机非劣效性试验。
Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 1 diabetes (QWINT-5): a phase 3 randomised non-inferiority trial.
机构信息
International Diabetes Center, HealthPartners Institute, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Department of Medicine, State University of New York Upstate Medical University, Syracuse, NY, USA.
出版信息
Lancet. 2024 Sep 21;404(10458):1132-1142. doi: 10.1016/S0140-6736(24)01804-X. Epub 2024 Sep 10.
BACKGROUND
Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This phase 3 study aimed to assess the efficacy and safety of efsitora compared with insulin degludec (degludec) in adults with type 1 diabetes.
METHODS
This randomised, 52-week, parallel-design, open-label, treat-to-target non-inferiority study conducted at 82 global health-care centres, randomly assigned (1:1) adults (ie, those aged ≥18 years) with type 1 diabetes glycated haemoglobin A (HbA) 7·0-10·0% (53·0-85·8 mmol/mol) to efsitora (n=343) or, degludec (n=349), both in combination with insulin lispro. The primary endpoint was the change in HbA from baseline to week-26 (non-inferiority margin=0·4%). The trial was registered at ClinicalTrials.gov (NCT05463744) and is completed.
FINDINGS
Between Aug 12, 2022, and May 7, 2024, of 893 participants enrolled, 692 (77%) participants were randomly assigned to once-weekly efsitora or once-daily degludec, and 623 (90%) participants completed the study. Mean HbA decreased from 7·88% (62·66 mmol/mol) at baseline to 7·41% (57·5 mmol/mol) at week 26 with efsitora and from 7·94% (63·3 mmol/mol) at baseline to 7·36% (56·9 mmol/mol) at week 26 with degludec. Mean HbA change from baseline to week 26 was -0·51% with efsitora and -0·56% with degludec (estimated treatment difference 0·052%, 95% CI -0·077 to 0·181; p=0·43), confirming a non-inferiority margin of 0·4% for efsitora compared with degludec. Rates of combined level 2 (<54 mg/dL [3·0 mmol/L]) or level 3 severe hypoglycaemia were higher with efsitora compared with degludec (14·03 vs 11·59 events per patient year of exposure; estimated rate ratio 1·21, 95% CI 1·04 to 1·41; p=0·016) during weeks 0-52, with the highest rates during weeks 0-12. Severe hypoglycaemia incidence was higher with efsitora (35 [10%] of 343) versus degludec (11 [3%] of 349) during weeks 0-52. Overall incidence of treatment-emergent adverse events was similar across treatment groups. One death not related to the study treatment occurred in the degludec group.
INTERPRETATION
In adults with type 1 diabetes, once-weekly efsitora showed non-inferior HbA reduction compared with daily insulin degludec. Higher rates of combined level 2 or level 3 hypoglycaemia and greater incidence of severe hypoglycaemia in participants treated with efsitora compared with participants treated with degludec might suggest the need for additional evaluation of efsitora dose initiation and optimisation in people with type 1 diabetes.
FUNDING
Eli Lilly and Company.
背景
胰岛素 efegrata（efegrata）是一种每周一次的基础胰岛素。这项 3 期研究旨在评估 efegrata 与胰岛素地特胰岛素（degludec）在 1 型糖尿病成人中的疗效和安全性。
方法
这项随机、52 周、平行设计、开放标签、以目标为导向的非劣效性研究在 82 个全球医疗中心进行，随机分配（1:1）年龄在 18 岁及以上的 1 型糖尿病患者（即年龄≥18 岁）糖化血红蛋白 A（HbA）7.0-10.0%（53.0-85.8mmol/mol）接受 efegrata（n=343）或 degludec（n=349）治疗，均与胰岛素赖脯肽联合使用。主要终点是从基线到第 26 周时 HbA 的变化（非劣效性边界=0.4%）。该试验在 ClinicalTrials.gov（NCT05463744）注册，现已完成。
结果
在 2022 年 8 月 12 日至 2024 年 5 月 7 日期间，893 名入组患者中，692 名（77%）患者被随机分配至每周一次的 efegrata 或每日一次的 degludec，623 名（90%）患者完成了研究。平均 HbA 从基线时的 7.88%（62.66mmol/mol）降至第 26 周时的 7.41%（57.5mmol/mol），接受 efegrata 治疗，从基线时的 7.94%（63.3mmol/mol）降至第 26 周时的 7.36%（56.9mmol/mol），接受 degludec 治疗。与 degludec 相比，efegrata 从基线到第 26 周的 HbA 变化为-0.51%，而 degludec 为-0.56%（估计治疗差异 0.052%，95%CI-0.077 至 0.181；p=0.43），证实 efegrata 与 degludec 相比非劣效性边界为 0.4%。与 degludec 相比，efegrata 组的联合 2 级（<54mg/dL[3.0mmol/L]）或 3 级严重低血糖发生率更高（暴露患者年分别为 14.03 次和 11.59 次；估计率比 1.21，95%CI 1.04-1.41；p=0.016），在 0-52 周时最高，在 0-12 周时最高。0-52 周期间，efegrata 组（35[10%]of343）发生严重低血糖的比例高于 degludec 组（11[3%]of349）。治疗期间发生的不良事件发生率在治疗组之间相似。在 degludec 组中，有 1 例与研究治疗无关的死亡事件发生。
结论
在 1 型糖尿病成人中，每周一次的 efegrata 与每日一次的地特胰岛素相比，HbA 降低非劣效。与 degludec 相比，接受 efegrata 治疗的患者联合 2 级或 3 级低血糖的发生率更高，严重低血糖的发生率更高，这可能表明需要进一步评估 1 型糖尿病患者中 efegrata 的起始剂量和优化。
资金来源
礼来公司。
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