Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Diabetes Obes Metab. 2020 Aug;22(8):1369-1377. doi: 10.1111/dom.14043. Epub 2020 Apr 28.
Chronic kidney disease (CKD) challenges diabetes management and is associated with increased cardiovascular morbidity and mortality. We examined whether clinical outcomes with insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (IDeg-100) are affected by renal function in a prespecified subgroup analysis from the BRIGHT trial.
BRIGHT (NCT02738151) was a multicentre, open-label, randomized, active-controlled, two-arm, parallel-group, 24-week study in insulin-naïve uncontrolled type 2 diabetes (T2D). Participants were randomized 1:1 to evening Gla-300 (n = 466) or IDeg-100 (n = 463) and stratified based on baseline estimated glomerular filtration rate (eGFR) for this analysis.
Heterogeneity of treatment effect across renal function subgroups was observed (P = .02), reflecting a greater mean glycated haemoglobin (HbA1c) reduction from baseline to week 24 with Gla-300 versus IDeg-100 in the eGFR <60 mL/min/1.73 m subgroup (least squares mean difference: -0.43% [95% confidence interval: -0.74% to -0.12%]), while there were no differences in hypoglycaemia incidence or rates over 24 weeks in that subgroup. HbA1c reductions were similar between treatments in the other eGFR subgroups. However, heterogeneity was observed for annualized rates of anytime (24 hours) or nocturnal (00:00-05:59 hours) confirmed hypoglycaemia (≤70 mg/dL [≤3.9 mmol/L]) over 24 weeks showing less hypoglycaemia with Gla-300 versus IDeg-100 in the ≥90 mL/min/1.73 m .
Kidney function seems to affect the glucose-lowering effects of Gla-300 versus IDeg-100 in insulin-naïve T2D. Greater HbA1c reductions with Gla-300 without increase in hypoglycaemia risk, were observed in patients with eGFR <60 mL/min/1.73 m .
慢性肾脏病（CKD）给糖尿病管理带来挑战，并与心血管发病率和死亡率的增加相关。我们通过 BRIGHT 试验的预先指定亚组分析，检查了胰岛素甘精 300 U/mL（Gla-300）和胰岛素德谷胰岛素 100 U/mL（IDeg-100）的临床结局是否受肾功能的影响。
BRIGHT（NCT02738151）是一项多中心、开放标签、随机、活性对照、双盲、平行组、24 周的研究，纳入了胰岛素初治未控制的 2 型糖尿病（T2D）患者。参与者按照基线估计肾小球滤过率（eGFR）进行 1:1 随机分配至晚间 Gla-300（n=466）或 IDeg-100（n=463）组，并进行分层。
观察到肾功能亚组之间治疗效果存在异质性（P=.02），反映了 eGFR <60 mL/min/1.73 m 亚组中，与 IDeg-100 相比，Gla-300 从基线到 24 周时平均糖化血红蛋白（HbA1c）降低更多（最小二乘均值差：-0.43%[95%置信区间：-0.74%至-0.12%]），而该亚组中 24 周内低血糖发生率或发生率没有差异。在其他 eGFR 亚组中，两种治疗方法的 HbA1c 降低情况相似。然而，在 24 周内任何时间（24 小时）或夜间（00:00-05:59 小时）证实的低血糖（≤70 mg/dL [≤3.9 mmol/L]）的年化发生率方面观察到了异质性，显示 Gla-300 与 IDeg-100 相比，在 eGFR ≥90 mL/min/1.73 m 亚组中低血糖发生更少。
肾功能似乎影响了胰岛素初治 T2D 患者中 Gla-300 与 IDeg-100 的降糖效果。在 eGFR <60 mL/min/1.73 m 亚组中，与 IDeg-100 相比，Gla-300 可使 HbA1c 降低更多，而低血糖风险没有增加。
