1 Division of Endocrinology and Metabolism, University of California San Diego School of Medicine , San Diego, California.
2 Center for Metabolic Research, VA San Diego Healthcare System , San Diego, California.
Diabetes Technol Ther. 2018 Nov;20(11):715-724. doi: 10.1089/dia.2018.0052. Epub 2018 Sep 14.
Glycated hemoglobin (HbA1c) and measures of short-term glycemia do not fully capture daily patterns in plasma glucose dynamics. This study evaluated 24-h glycemic profiles in patients with type 2 diabetes (T2D) initiated on dapagliflozin treatment using continuous glucose monitoring (CGM).
This randomized double-blind placebo-controlled multicenter parallel-design 4-week study compared dapagliflozin (10 mg/d; n = 50) with placebo (n = 50) in adult patients with T2D uncontrolled (HbA1c 7.5%-10.5%) on either stable doses of metformin monotherapy (≥1500 mg/d) or insulin (≥30 U/d with or without up to two oral antidiabetes drugs). CGM was used to measure 24-h glycemic profiles for 7 days pretreatment and during week 4 of treatment. The primary outcome was change from baseline in 24-h mean glucose (MG) at week 4.
The 24-h MG decreased 18.2 mg/dL with dapagliflozin and increased 5.8 mg/dL with placebo (P < 0.001). The proportion of time spent in the target glucose range (70-180 mg/dL) increased significantly with dapagliflozin versus placebo (69.6% vs. 52.9%; P < 0.001), with a small (0.3%) increase in time spent in the hypoglycemic range (<70 mg/dL), driven by those on background insulin therapy. Dapagliflozin reduced postprandial glucose and significantly decreased overall glucose variability. Few events of symptomatic hypoglycemia occurred. The most common adverse event was urinary tract infection (6% in each treatment arm).
Compared with placebo, dapagliflozin improved measures of glycemic control and variability as assessed by CGM. Glycemic improvements were more pronounced in the group on background metformin than those receiving basal insulin.
糖化血红蛋白（HbA1c）和短期血糖测量并不能完全捕捉到血浆葡萄糖动力学的日常变化。本研究使用连续血糖监测（CGM）评估了接受达格列净治疗的 2 型糖尿病（T2D）患者的 24 小时血糖谱。
这项随机、双盲、安慰剂对照、多中心、平行设计的 4 周研究比较了达格列净（10mg/d；n=50）与安慰剂（n=50）在 T2D 患者中的疗效，这些患者在稳定剂量的二甲双胍单药治疗（≥1500mg/d）或胰岛素治疗（≥30U/d，联合或不联合最多两种口服抗糖尿病药物）下血糖控制不佳（HbA1c 7.5%-10.5%）。CGM 用于测量治疗前 7 天和治疗第 4 周的 24 小时血糖谱。主要结局是第 4 周时 24 小时平均血糖（MG）的基线变化。
与安慰剂相比，达格列净使 24 小时 MG 降低了 18.2mg/dL，而安慰剂使 24 小时 MG 升高了 5.8mg/dL（P<0.001）。与安慰剂相比，达格列净使目标血糖范围内（70-180mg/dL）的时间比例显著增加（69.6% vs. 52.9%；P<0.001），而接受背景胰岛素治疗的患者低血糖范围（<70mg/dL）的时间略有增加（0.3%）。达格列净降低了餐后血糖，显著降低了总体血糖变异性。低血糖症状很少发生。最常见的不良事件是尿路感染（各治疗组均为 6%）。
与安慰剂相比，达格列净改善了 CGM 评估的血糖控制和变异性。在接受背景二甲双胍治疗的患者中，血糖改善更为明显，而接受基础胰岛素治疗的患者则不明显。
