解放军总医院第一医学中心母义明主任医师团队比较了每周一次胰岛素Icodec与每日一次德古胰岛素治疗胰岛素缺乏型2型糖尿病的疗效与安全性。相关论文于2023年6月24日发表在《美国医学会杂志》上。

对于2型糖尿病患者，每周一次的胰岛素icodec可以提供一种比每日基础胰岛素更简单的剂量替代方案。

为了评价每周一次icodec与每日一次德古胰岛素治疗胰岛素缺乏型2型糖尿病的疗效和安全性，2021年3月至2022年6月，研究组在11个国家的92个机构对血红蛋白A_1c（HbA_1c）为7%-11%（53-97 mmol/mol）的任何非胰岛素降血糖剂治疗的2型糖尿病成年人进行了一项随机、双盲、非劣效、靶向治疗的3a期临床试验。将参与者以1:1的比例随机分配接受每周一次的icodec和每天一次的安慰剂（icodec组；n = 294）或每天一次的德古胰岛素和每周一次的安慰剂（去甲肾上腺素组；n = 294）。

主要终点是从基线到第26周HbA_1c的变化（非劣效性界限，0.3%的百分点）。次要终点包括从基线到第26周的空腹血糖变化、治疗最后2周的每周平均胰岛素剂量、从基线到26周的体重变化以及2级（临床意义重大；葡萄糖水平<54 mg/dL）和3级（严重；需要外部协助恢复）低血糖发作次数。

在588名随机参与者中（平均年龄58岁；219名[37%]女性），564人（96%）完成了试验。在26周时，icodec组的平均HbA_1c水平从8.6%（观察到）下降到7.0%（估计），而德古胰岛素组从8.5%（观察到）下降到7.2%（估计）（估计治疗差异为−0.2个百分点），证实了非劣效性（P < .001）和优越性（P = .002）。

从基线到第26周，icodec组和德古胰岛素组的空腹血糖变化（ETD为0mg/dL；P = .90）、治疗最后2周的平均每周胰岛素剂量，或从基线到第26周的体重变化（2.8 kg vs 2.3 kg；ETD为0.46 kg；P = .17）均没有显著差异 。从第0周到第31周，icodec组的2或3级低血糖综合发生率在数值上高于德古胰岛素组（每患者-年暴露0.31次vs 0.15次事件；P = .11）。 在第0周至第26周，icodec组的发病率在统计学上更高（每患者-年暴露0.35次vs 0.12次；P = .01）。

研究结果表明，在胰岛素缺乏型2型糖尿病患者中，治疗26周后，每周一次的icodec显示出比每天一次的德古胰岛素更好的HbA_1c降低，在两组患者每年暴露少于1次的情况下，体重变化没有差异，合并2或3级低血糖事件的发生率更高。

附：英文原文

Title: Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial

Author: Ildiko Lingvay, Marisse Asong, Cyrus Desouza, Pierre Gourdy, Soumitra Kar, André Vianna, Tina Vilsbll, Siri Vinther, Yiming Mu

Issue&Volume: 2023-06-24

Abstract:

Importance  Once-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes.

Objective  To evaluate the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes.

Design, Setting, and Participants  Randomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any noninsulin glucose-lowering agents with hemoglobin A1c (HbA1c) of 7%-11% (53-97 mmol/mol).

Interventions  Participants were randomly assigned in a 1:1 ratio to receive either once-weekly icodec and once-daily placebo (icodec group; n=294) or once-daily degludec and once-weekly placebo (degludec group; n=294).

Main Outcomes and Measures  The primary end point was change in HbA1c from baseline to week 26 (noninferiority margin, 0.3% percentage points). Secondary end points included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, body weight change from baseline to week 26, and number of level 2 (clinically significant; glucose level <54 mg/dL) and level 3 (severe; requiring external assistance for recovery) hypoglycemic episodes.

Results  Among 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. Mean HbA1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the icodec group and from 8.5% (observed) to 7.2% (estimated) in the degludec group (estimated treatment difference [ETD], 0.2 [95% CI, 0.3 to 0.1] percentage points), confirming noninferiority (P<.001) and superiority (P=.002). There were no significant differences between the icodec and degludec groups for fasting plasma glucose change from baseline to week 26 (ETD, 0 [95% CI, 6 to 5] mg/dL; P=.90), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs 2.3 kg; ETD, 0.46 [95% CI, 0.19 to 1.10] kg; P=.17). Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than the degludec group from week 0 to 31 (0.31 vs 0.15 events per patient-year exposure; P=.11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs 0.12 events per patient-year exposure; P=.01).

Conclusions and Relevance  Among people with insulin-naive type 2 diabetes, once-weekly icodec demonstrated superior HbA1c reduction to once-daily degludec after 26 weeks of treatment, with no difference in weight change and a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient-year exposure in both groups.

DOI: 10.1001/jama.2023.11313

Source: https://jamanetwork.com/journals/jama/fullarticle/2806635