Chamarthi Bindu, Cincotta Anthony H
a VeroScience LLC , Tiverton , RI , USA.
b Division of Endocrinology , Diabetes and Hypertension, Brigham and Women's Hospital , Boston , MA , USA.
Postgrad Med. 2017 May;129(4):446-455. doi: 10.1080/00325481.2017.1315290. Epub 2017 Apr 12.
The concurrent use of an insulin sensitizer in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control on basal-bolus insulin may help improve glycemic control while limiting further insulin requirement. Bromocriptine-QR (B-QR), a quick release, sympatholytic, dopamine D2 receptor agonist therapy for T2DM, is a postprandial insulin sensitizer. This study evaluated the effect of B-QR on dysglycemia in T2DM subjects with suboptimal glycemic control on basal-bolus insulin plus metformin.
The effect of once-daily morning administration of B-QR on dysglycemia was evaluated in 60 T2DM subjects derived from the Cycloset Safety Trial, with HbA1c >7% on basal-bolus insulin plus metformin at baseline, randomized to B-QR (N = 44) versus placebo (N = 16) and completed 12 weeks of study drug treatment. The analyses also included a subset of subjects on high-dose insulin (total daily insulin dose (TDID) ≥70 units; N = 36: 27 B-QR; 9 placebo).
Subjects were well matched at baseline. After 12 weeks of B-QR treatment, mean % HbA1c decreased by -0.73% relative to baseline (p < 0.001) and by -1.13 relative to placebo (p < 0.001). In the high-dose insulin subset, B-QR therapy resulted in % HbA1c reductions of -0.95 and -1.49 relative to baseline (p < 0.001) and placebo (p = 0.001) respectively. Secondary analyses of treatment effect at 24 and 52 weeks demonstrated similar influences of B-QR on HbA1c. The fasting plasma glucose (FPG) and TDID changes within each treatment group were not significant. More subjects achieved HbA1c ≤7 at 12 weeks with B-QR relative to placebo (36.4% B-QR vs 0% placebo, Fisher's exact 2-sided p = 0.003 in the entire cohort and 37% vs 0%, 2-sided p = 0.039 in the high-dose insulin subset).
B-QR therapy improves glycemic control in T2DM subjects whose glycemia is poorly controlled on metformin plus basal-bolus insulin, including individuals on high-dose basal-bolus insulin. This glycemic impact occurred without significant change in FPG, suggesting a postprandial glucose lowering mechanism of action. Cycloset Safety Trial registration: ClinicalTrials.gov Identifier: NCT00377676.
对于基础-餐时胰岛素治疗血糖控制不佳的2型糖尿病（T2DM）患者，同时使用胰岛素增敏剂可能有助于改善血糖控制，同时限制进一步的胰岛素需求。溴隐亭-QR（B-QR）是一种用于T2DM的速释、抗交感神经、多巴胺D2受体激动剂疗法，是一种餐后胰岛素增敏剂。本研究评估了B-QR对基础-餐时胰岛素加二甲双胍治疗血糖控制欠佳的T2DM患者血糖异常的影响。
在来自Cycloset安全性试验的60例T2DM患者中评估每日清晨一次服用B-QR对血糖异常的影响，这些患者在基线时基础-餐时胰岛素加二甲双胍治疗下HbA1c>7%，随机分为B-QR组（N = 44）和安慰剂组（N = 16），并完成12周的研究药物治疗。分析还包括一部分高剂量胰岛素治疗的患者（每日胰岛素总剂量（TDID）≥70单位；N = 36：27例B-QR组；9例安慰剂组）。
受试者在基线时匹配良好。B-QR治疗12周后，平均HbA1c百分比相对于基线下降了-0.73%（p < 0.001），相对于安慰剂下降了-1.13（p < 0.001）。在高剂量胰岛素亚组中，B-QR治疗导致HbA1c百分比相对于基线分别下降了-0.95和-1.49（p < 0.001），相对于安慰剂下降了-1.49（p = 0.001）。24周和52周治疗效果的二次分析显示B-QR对HbA1c有类似影响。每个治疗组内的空腹血糖（FPG）和TDID变化不显著。与安慰剂相比，更多接受B-QR治疗的受试者在12周时HbA1c≤7（整个队列中B-QR组为36.4%，安慰剂组为0%，Fisher精确双侧p = 0.003；高剂量胰岛素亚组中为37%对0%，双侧p = 0.039）。
B-QR治疗可改善二甲双胍加基础-餐时胰岛素治疗血糖控制不佳的T2DM患者的血糖控制，包括使用高剂量基础-餐时胰岛素的个体。这种血糖影响在FPG无显著变化的情况下发生，提示其作用机制为降低餐后血糖。Cycloset安全性试验注册信息：ClinicalTrials.gov标识符：NCT00377676。
