Rosenstock Julio, Bailey Timothy, Connery Lisa, Miller Eden, Desouza Cyrus, Wang Qianqian, Leohr Jennifer, Knights Alastair, Carr Molly C, Child Christopher J
Velocity Clinical Research at Medical City, Dallas.
Headlands Research AMCR Institute, Escondido, CA.
N Engl J Med. 2025 Jul 24;393(4):325-335. doi: 10.1056/NEJMoa2502796. Epub 2025 Jun 22.
In previous treat-to-target trials, adjustments to the dose of basal insulin have been made at least weekly, according to fasting blood glucose levels. A fixed-dose regimen of insulin efsitora alfa (efsitora), a once-weekly basal insulin, may provide a benefit in adults with type 2 diabetes who have not received previous insulin therapy.
We conducted a 52-week, phase 3, open-label, treat-to-target trial involving adults with type 2 diabetes who had not previously received insulin therapy. Participants were randomly assigned in a 1:1 ratio to receive once-weekly efsitora or once-daily insulin glargine U100 (glargine). Treatment with efsitora was initiated as a single dose of 100 U administered once weekly, with dose adjustments made every 4 weeks, as needed, at fixed doses of 150, 250, and 400 U to achieve fasting blood glucose levels of 80 to 130 mg per deciliter. Doses of glargine were adjusted weekly or more often according to a standard algorithm to reach the same glycemic goals. The primary end point, tested for noninferiority (noninferiority margin, 0.4 percentage points), was the change from baseline in the glycated hemoglobin level at 52 weeks.
A total of 795 participants underwent randomization. The mean glycated hemoglobin level decreased from 8.20% at baseline to 7.05% at week 52 with efsitora (least-squares mean change, -1.19 percentage points) and from 8.28% to 7.08% with glargine (least-squares mean change, -1.16 percentage points); the estimated between-group difference of -0.03 percentage points (95% confidence interval [CI], -0.18 to 0.12) confirmed the noninferiority of efsitora to glargine. Superiority was not shown (P = 0.68). The rate of combined clinically significant hypoglycemia (glucose level, <54 mg per deciliter) or severe hypoglycemia (level 3; requiring assistance for treatment) was lower with efsitora than with glargine (0.50 events per participant-year of exposure with efsitora vs. 0.88 with glargine; estimated rate ratio, 0.57 [95% CI, 0.39 to 0.84]). At week 52, the mean total weekly insulin dose was 289.1 U per week with efsitora and 332.8 U per week with glargine (estimated between-group difference, -43.7 U per week; 95% CI, -62.4 to -25.0); the median number of dose adjustments needed was 2 with efsitora and 8 with glargine.
In adults with type 2 diabetes who had not previously received insulin, once-weekly efsitora, administered in a fixed-dose regimen, was noninferior to once-daily glargine in reducing glycated hemoglobin levels. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT05662332.).
在之前的达标治疗试验中，根据空腹血糖水平，至少每周对基础胰岛素剂量进行调整。胰岛素efsitola alfa（efsitora）是一种每周一次的基础胰岛素，固定剂量方案可能对未接受过胰岛素治疗的2型糖尿病成人患者有益。
我们进行了一项为期52周的3期开放标签达标治疗试验，纳入未接受过胰岛素治疗的2型糖尿病成人患者。参与者按1:1比例随机分配，接受每周一次的efsitora或每日一次的甘精胰岛素U100（甘精胰岛素）。efsitora治疗起始剂量为每周一次100 U，根据需要每4周进行一次剂量调整，固定剂量为150、250和400 U，以使空腹血糖水平达到80至130 mg/分升。甘精胰岛素的剂量根据标准算法每周或更频繁地调整，以达到相同的血糖目标。主要终点为52周时糖化血红蛋白水平相对于基线的变化，进行非劣效性检验（非劣效界值为0.4个百分点）。
共有795名参与者被随机分组。使用efsitora时，糖化血红蛋白水平从基线时的8.20%降至第52周时的7.05%（最小二乘均值变化为-1.19个百分点）；使用甘精胰岛素时，从8.28%降至7.08%（最小二乘均值变化为-1.16个百分点）；估计组间差异为-0.03个百分点（95%置信区间[CI]，-0.18至0.12），证实了efsitora不劣于甘精胰岛素。未显示出优效性（P = 0.68）。efsitora组联合具有临床意义的低血糖（血糖水平<54 mg/分升）或严重低血糖（3级；需要治疗协助）的发生率低于甘精胰岛素组（efsitora组每暴露参与者年0.50次事件，甘精胰岛素组为0.88次；估计发生率比为0.57 [95% CI，0.39至0.84]）。在第52周时，efsitora组每周平均总胰岛素剂量为289.1 U，甘精胰岛素组为332.8 U（估计组间差异为每周-43.7 U；95% CI，-62.4至-25.0）；efsitora组所需剂量调整的中位数为2次，甘精胰岛素组为8次。
在未接受过胰岛素治疗的2型糖尿病成人患者中，采用固定剂量方案每周一次给予efsitora在降低糖化血红蛋白水平方面不劣于每日一次的甘精胰岛素。（由礼来公司资助；ClinicalTrials.gov编号，NCT05662332。）
