美国Velocity医药公司Julio Rosenstock比较了每周Icodec胰岛素与每天甘精U100治疗2型糖尿病的疗效与安全性。相关论文发表在2023年6月24日出版的《新英格兰医学杂志》上。

icodec胰岛素是一种用于糖尿病管理的每周一次的基础胰岛素类似物。

研究组进行了一项为期78周的随机、开放标签、靶向治疗的3a期临床试验（包括52周的主期和26周的延长期，外加5周的随访期），招募既往未接受胰岛素治疗的2型糖尿病（糖化血红蛋白水平，7%至11%）成年人。参与者以1:1的比例被随机分配接受每周一次的胰岛素icodec或每天一次的甘精胰岛素U100。主要终点是糖化血红蛋白水平从基线到第52周的变化；验证性次要终点是第48至52周血糖在70至180毫克/分升（3.9至10.0毫摩尔/升）范围内的时间百分比。记录低血糖发作（从基线到第52周和第83周）。

每组包括492名参与者。两组患者的基线特征相似。52周时，icodec组的糖化血红蛋白水平平均下降幅度大于甘精U100（icodec从8.50%下降到6.93%[平均变化，−1.55个百分点]，甘精U100从8.44%下降到7.12%[平均变化−1.35个百分点]）；估计组间差异为-0.19个百分点，证实了icodec的非劣效性（P<0.001）和优越性（P=0.02）。使用icodec的患者在每分升70至180毫克的血糖范围内的时间百分比显著高于甘精U100（71.9%对66.9%；估计组间差异为4.27个百分点；P<0.001），这证实了其优越性。

在第52周，联合临床显著或严重低血糖的发生率分别为每人-年0.30次icodec暴露事件和0.16次甘精U100暴露事件（估计比率为1.64），以及第83周每人-年分别0.30次和0.16例暴露事件（估计比率为1.63）。没有发现新的安全性信号，两组的不良事件发生率相似。

研究结果表明，每周一次的胰岛素icodec比每天一次的甘精胰岛素U100对血糖的控制明显更好。

附：英文原文

Title: Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin | NEJM

Author: Julio Rosenstock, M.D.,, Stephen C. Bain, F.R.C.P.,, Amoolya Gowda, M.D.,, Esteban Jódar, M.D., Ph.D.,, Bo Liang, M.D., Ph.D.,, Ildiko Lingvay, M.D., M.P.H., M.S.C.S.,, Tomoyuki Nishida, M.Sc,, Roberto Trevisan, M.D., Ph.D.,, and Ofri Mosenzon, M.D.

Issue&Volume: 2023-06-24

Abstract:

Background

Insulin icodec is an investigational once-weekly basal insulin analogue for diabetes management.

Methods

We conducted a 78-week randomized, open-label, treat-to-target phase 3a trial (including a 52-week main phase and a 26-week extension phase, plus a 5-week follow-up period) involving adults with type 2 diabetes (glycated hemoglobin level, 7 to 11%) who had not previously received insulin. Participants were randomly assigned in a 1:1 ratio to receive once-weekly insulin icodec or once-daily insulin glargine U100. The primary end point was the change in the glycated hemoglobin level from baseline to week 52; the confirmatory secondary end point was the percentage of time spent in the glycemic range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) in weeks 48 to 52. Hypoglycemic episodes (from baseline to weeks 52 and 83) were recorded.

Results

Each group included 492 participants. Baseline characteristics were similar in the two groups. The mean reduction in the glycated hemoglobin level at 52 weeks was greater with icodec than with glargine U100 (from 8.50% to 6.93% with icodec [mean change, 1.55 percentage points] and from 8.44% to 7.12% with glargine U100 [mean change, 1.35 percentage points]); the estimated between-group difference (0.19 percentage points; 95% confidence interval [CI], 0.36 to 0.03) confirmed the noninferiority (P<0.001) and superiority (P=0.02) of icodec. The percentage of time spent in the glycemic range of 70 to 180 mg per deciliter was significantly higher with icodec than with glargine U100 (71.9% vs. 66.9%; estimated between-group difference, 4.27 percentage points [95% CI, 1.92 to 6.62]; P<0.001), which confirmed superiority. Rates of combined clinically significant or severe hypoglycemia were 0.30 events per person-year of exposure with icodec and 0.16 events per person-year of exposure with glargine U100 at week 52 (estimated rate ratio, 1.64; 95% CI, 0.98 to 2.75) and 0.30 and 0.16 events per person-year of exposure, respectively, at week 83 (estimated rate ratio, 1.63; 95% CI, 1.02 to 2.61). No new safety signals were identified, and incidences of adverse events were similar in the two groups.

Conclusions

Glycemic control was significantly better with once-weekly insulin icodec than with once-daily insulin glargine U100.

DOI: 10.1056/NEJMoa2303208

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2303208