恩格列净治疗1型糖尿病8周开放标签概念验证试验期间的日间血糖模式
Diurnal Glycemic Patterns during an 8-Week Open-Label Proof-of-Concept Trial of Empagliflozin in Type 1 Diabetes.
作者信息
Perkins Bruce A, Cherney David Z I, Soleymanlou Nima, Lee Justin A, Partridge Helen, Tschirhart Holly, Zinman Bernard, Mazze Roger, Fagan Nora, Kaspers Stefan, Woerle Hans-Juergen, Broedl Uli C, Johansen Odd Erik
机构信息
Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
出版信息
PLoS One. 2015 Nov 6;10(11):e0141085. doi: 10.1371/journal.pone.0141085. eCollection 2015.
BACKGROUND
We recently reported improved glycemic control with reduced insulin dose in subjects with type 1 diabetes treated with the sodium glucose co-transporter-2 inhibitor empagliflozin. To further characterize the effects, we analyzed diurnal glycemic patterns by continuous glucose monitoring (CGM).
METHODS
In an 8-week single-arm open-label pilot study of empagliflozin, we compared ambulatory glucose profiles produced from CGM data during 2-week intervals in a placebo run-in baseline period, end-of-treatment, and post-treatment. Change in glycemic exposure was evaluated by area under the median curve according to time of day (AUCTOTAL 12:00am-11:55pm; AUCDAY 7:05am-10:55pm, AUCNIGHT 11:00pm-7:00am), as well as glycemic variability, glycemic stability and time-in-target (≥70 to ≤140mg/dL).
RESULTS
The 40 patients (26 on insulin pump) were aged 24±5 years and BMI 24.5±3.2 kg/m2. Consistent with the observed HbA1c decrease (8.0±0.9% to 7.6±0.9%, p<0.0001), normalized AUCTOTAL CGM decreased from 153.7±25.4 to 149.0±30.2mg/dL∙h at end-of-treatment (p = 0.31), and significantly increased post-treatment (164.1±29.5mg/dL∙h, p = 0.02). The numerical decrease in normalized AUCNIGHT (152.0±36.6 to 141.9±34.4mg/dL∙h, p = 0.13) exceeded AUCDAY (154.5±24.5 to 152.6±30.4mg/dL∙h, p = 0.65). Trends toward lower glycemic variability (83.1±18.9 to 75.6±28.6mg/dL, p = 0.06) and little change in glycemic stability (10.8±3.6 to 10.3±4.5mg/dL/h, p = 0.51) were observed. When empagliflozin was discontinued, these worsened relative to baseline (89.3±19.3mg/dL, p = 0.04 and 11.8±3.7mg/dL/hr, p = 0.08). Time-in-target numerically increased (40.2±11.9 to 43.1±13.5%, p = 0.69) at end-of-treatment but reversed post-treatment. Findings were similar on stratification of pump and MDI subjects.
CONCLUSIONS
We observed that empagliflozin was associated with patterns of improved nighttime glycemia more prominent than daytime.
TRIAL REGISTRATION
Clinicaltrials.gov NCT01392560.
背景
我们最近报告称，在使用钠-葡萄糖协同转运蛋白2抑制剂恩格列净治疗的1型糖尿病患者中，血糖控制得到改善，胰岛素剂量减少。为了进一步描述其效果，我们通过持续葡萄糖监测（CGM）分析了昼夜血糖模式。
方法
在一项为期8周的恩格列净单臂开放标签试验性研究中，我们比较了在安慰剂导入基线期、治疗结束时和治疗后，每2周间隔期间CGM数据产生的动态血糖谱。根据一天中的时间，通过中位数曲线下面积评估血糖暴露的变化（AUCTOTAL上午12:00至晚上11:55；AUCDAY上午7:05至晚上10:55，AUCNIGHT晚上11:00至上午7:00），以及血糖变异性、血糖稳定性和达标时间（≥70至≤140mg/dL）。
结果
40例患者（26例使用胰岛素泵），年龄24±5岁，体重指数24.5±3.2kg/m²。与观察到的糖化血红蛋白降低情况一致（从8.0±0.9%降至7.6±0.9%，p<0.0001），治疗结束时，标准化的CGM AUCTOTAL从153.7±25.4降至149.0±30.2mg/dL∙h（p = 0.31），治疗后显著增加（164.1±29.5mg/dL∙h，p = 0.02）。标准化的AUCNIGHT数值下降（从152.0±36.6降至141.9±34.4mg/dL∙h，p = 0.13）超过了AUCDAY（从154.5±24.5降至152.6±30.4mg/dL∙h，p = 0.65）。观察到血糖变异性有降低趋势（从83.1±18.9降至75.6±28.6mg/dL，p = 0.06），血糖稳定性变化不大（从10.8±3.6降至10.3±4.5mg/dL/h，p = 0.51）。当停用恩格列净时，这些指标相对于基线恶化（分别为89.3±19.3mg/dL，p = 0.04和11.8±3.7mg/dL/hr，p = 0.08）。治疗结束时达标时间数值增加（从40.2±11.9增至43.1±13.5%，p = 0.69），但治疗后逆转。在胰岛素泵和多次皮下注射胰岛素（MDI）治疗的患者分层分析中，结果相似。
结论
我们观察到，恩格列净与夜间血糖改善模式相关，且这种改善比白天更为显著。
试验注册
Clinicaltrials.gov NCT01392560。
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