在2型糖尿病预治疗亚表型中，基础胰岛素甘精胰岛素（300 U/mL和100 U/mL）联合或不联合餐时胰岛素的疗效：一项事后分析的见解

Responses to Basal Insulin Glargine (300 U/mL and 100 U/mL) with or Without Pre-prandial Insulin in Pre-treated Subphenotypes of Type 2 Diabetes: Insights from a Post Hoc Analysis.

作者信息

Landgraf Wolfgang, Owens David R, Frier Brian M, Bolli Geremia B

机构信息

Medical Department, Diabetes Franchise General Medicines, Sanofi, Frankfurt, Germany.

Sanofi-Aventis Deutschland GmbH, c/o Oskar Helene Park 33, 14195, Berlin, Germany.

出版信息

Diabetes Ther. 2024 Aug;15(8):1769-1784. doi: 10.1007/s13300-024-01608-4. Epub 2024 Jun 15.

INTRODUCTION

This study aimed to evaluate glycemic outcomes in subphenotypes of type 2 diabetes (T2D) with HbA1c > 7.0%, previously on basal insulin (pre-BI) alone (≥ 42 U/day) or on basal-bolus therapy (pre-BB), and who were switched to either basal insulin glargine 300 U/mL (IGlar-300) or 100 U/mL (IGlar-100), with or without pre-prandial insulin.

METHODS

Participants from EDITION 2 (pre-BI, n = 785), and EDITION 1 (pre-BB, n = 792) trials were assigned retrospectively to subphenotypes of T2D: severe insulin deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity diabetes (MOD), and severe insulin resistant diabetes (SIRD). Key efficacy and safety parameters were analyzed at baseline, and after 26 weeks, for IGlar-300 and IGlar-100 pooled groups according to subphenotypes. Outcomes were also compared with insulin-naïve subphenotypes on oral antihyperglycemic drugs (OADs) from the EDITION 3 trial (pre-OAD, n = 858).

RESULTS

Pre-BI and pre-BB treated subphenotypes with SIDD had a higher mean HbA1c (8.9% and 9.1%) at baseline compared to those of MARD (7.7% and 7.8%) and MOD (8.1% and 8.2%) and after 26 weeks remained above target HbA1c (7.7% and 8.0%) despite mean glargine doses of 0.7 to 1.0 U/kg/day and pre-prandial insulin use in the pre-BB SIDD subgroup. Pre-BB treated individuals with MARD and MOD achieved lower HbA1c levels (6.9% and 7.2%) than the pre-BI groups (7.3% and 7.5%) despite similar mean FPG levels (123-130 mg/dL). Only 19-22% of participants with SIDD achieved HbA1c < 7.0% compared to 33-51% with MARD and MOD, respectively. Pre-BI and pre-BB treated subphenotypes experienced more hypoglycemia than pre-OAD treated subphenotypes.

CONCLUSION

Individuals with T2D assigned post hoc to the SIDD subphenotype achieved suboptimal glycemic control with glargine regimens including basal-bolus therapy, alerting clinicians to improve further diabetes treatment, particularly post-prandial glycemic control, in individuals with SIDD.

引言

本研究旨在评估糖化血红蛋白（HbA1c）>7.0%、之前仅接受基础胰岛素治疗（预基础胰岛素治疗，pre-BI，≥42 U/天）或基础-餐时胰岛素治疗（预基础-餐时治疗，pre-BB），且改为接受甘精胰岛素300 U/mL（IGlar-300）或100 U/mL（IGlar-100）治疗（无论是否联用餐时胰岛素）的2型糖尿病（T2D）亚表型患者的血糖结局。

方法

来自EDITION 2试验（预基础胰岛素治疗组，n = 785）和EDITION 1试验（预基础-餐时治疗组，n = 792）的参与者被回顾性地分为T2D亚表型：严重胰岛素缺乏型糖尿病（SIDD）、轻度年龄相关性糖尿病（MARD）、轻度肥胖型糖尿病（MOD）和严重胰岛素抵抗型糖尿病（SIRD）。根据亚表型，在基线时以及26周后，对IGlar-300和IGlar-100合并组的关键疗效和安全性参数进行分析。还将结局与来自EDITION 3试验（预口服降糖药治疗组，pre-OAD，n = 858）的未接受过胰岛素治疗、使用口服降糖药（OADs）的亚表型进行比较。

结果

与MARD（7.7%和7.8%）和MOD（8.1%和8.2%）相比，预基础胰岛素治疗组和预基础-餐时治疗组中SIDD亚表型患者在基线时的平均HbA1c水平更高（分别为8.9%和9.1%），并且在26周后尽管预基础-餐时治疗组的SIDD亚组平均甘精胰岛素剂量为0.7至1.0 U/kg/天且使用了餐时胰岛素，但仍高于目标HbA1c水平（7.7%和8.0%）。尽管平均空腹血糖水平相似（123 - 130 mg/dL），但接受预基础-餐时治疗的MARD和MOD患者的HbA1c水平（分别为6.9%和7.2%）低于预基础胰岛素治疗组（分别为7.3%和7.5%）。与MARD和MOD患者分别有33% - 51%达到HbA1c <7.0%相比，只有19% - 22%的SIDD患者达到该目标。预基础胰岛素治疗组和预基础-餐时治疗组的亚表型患者比预口服降糖药治疗组的亚表型患者经历了更多的低血糖事件。