Laviola Luigi, Porcellati Francesca, Bruttomesso Daniela, Larosa Monica, Rossi Maria Chiara, Nicolucci Antonio
Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
Section of Internal Medicine, Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Perugia, Italy.
Diabetes Ther. 2021 Feb;12(2):509-525. doi: 10.1007/s13300-020-00982-z. Epub 2020 Dec 22.
Following pivotal trials, real-world evidence is important to assess the impact of new drugs in everyday clinical practice. The RESTORE-1 study aimed to compare effectiveness and safety of the second-generation basal insulins (2BI), i.e., insulin glargine 300 U/ml (Gla-300) vs. degludec 100 U/ml (IDeg-100), in type 1 diabetes (T1D).
Retrospective, non-inferiority, multicenter study, based on electronic medical records. All patients switching to Gla-300 or IDeg-100 from first-generation basal insulins (1BI) were 1:1 propensity score matched (PSM). Changes during 6 months in HbA1c (primary endpoint), fasting plasma glucose (FPG), body weight, and insulin doses were assessed using linear mixed models for repeated measures. Incidence rates (IR) of hypoglycemic events were assessed.
Overall, 19 centers provided data on 585 patients in each PSM cohort. For both groups, statistically significant reductions in HbA1c from baseline to 6 months were documented: - 0.20%; (95% CI - 0.32; - 0.08) in the Gla-300 group and - 0.14%; (95% CI - 0.24; - 0.04) in the IDeg-100 group. The non-inferiority of Gla-300 vs. IDeg-100 was confirmed (non-inferiority margin of 0.30%; upper 95% CI at 6 months, 0.09%). No statistically significant between-group differences emerged in FPG and body weight. Dose changes of basal and short-acting insulin were small in both groups, but higher in the Gla-300 group than in the Deg-100 group (p < 0.006). Incidence rates (IR) of hypoglycemia (blood glucose ≤ 70 mg/dl and < 54 mg/dl) during the 6-month follow-up by treatment were slightly lower in the Gla-300 group than in the Deg-100 group [IR ratios 0.82 (95% CI 0.55; 1.22) and 0.83; (95% CI 0.38; 1.83), respectively]. Hypoglycemic events (blood glucose < 54 mg/dl) decreased at 6 months in both groups (p = 0.01 for Gla-300 and p < 0.001 for IDeg-100). There were no severe hypoglycemic events for Gla-300 and seven events for IDeg-100 (p = 0.02).
Switching from 1BI to 2BI in adults with T1D was associated with similar improvements in glycemic control and overall significant decrease in hypoglycemia, with no severe events with Gla-300. Effectiveness of both insulins was limited by under-titration.
在关键试验之后，真实世界证据对于评估新药在日常临床实践中的影响非常重要。RESTORE-1研究旨在比较第二代基础胰岛素（2BI），即甘精胰岛素300 U/ml（Gla-300）与德谷胰岛素100 U/ml（IDeg-100）在1型糖尿病（T1D）中的有效性和安全性。
基于电子病历的回顾性、非劣效性、多中心研究。所有从第一代基础胰岛素（1BI）转换为Gla-300或IDeg-100的患者按1:1倾向评分匹配（PSM）。使用重复测量的线性混合模型评估6个月内糖化血红蛋白（主要终点）、空腹血糖（FPG）、体重和胰岛素剂量的变化。评估低血糖事件的发生率（IR）。
总体而言，19个中心提供了每个PSM队列中585例患者的数据。两组均记录到从基线到6个月糖化血红蛋白有统计学意义的降低：Gla-300组为-0.20%；（95%CI -0.32；-0.08），IDeg-100组为-0.14%；（95%CI -0.24；-0.04）。证实了Gla-300相对于IDeg-100的非劣效性（非劣效性界值为0.30%；6个月时95%CI上限为0.09%）。FPG和体重在组间无统计学意义的差异。两组基础胰岛素和短效胰岛素的剂量变化都很小，但Gla-300组高于Deg-100组（p<0.006）。治疗期间6个月随访时低血糖（血糖≤70 mg/dl和<54 mg/dl）的发生率在Gla-300组略低于IDeg-100组[IR比分别为0.82（95%CI 0.55；1.22）和0.83；（95%CI 0.38；1.83）]。两组在6个月时低血糖事件（血糖<54 mg/dl）均减少（Gla-300组p=0.01，IDeg-100组p<0.001）。Gla-300组无严重低血糖事件，IDeg-100组有7例（p=0.02）。
T1D成人从1BI转换为2BI与血糖控制的相似改善以及低血糖总体显著降低相关，Gla-300组无严重事件。两种胰岛素的有效性均受剂量调整不足的限制。
