OBJECTIVE ITCA 650 is a subdermal osmotic mini-pump that continuously delivers exenatide subcutaneously for 3–6 months. The efficacy, safety, and tolerability of ITCA 650 added to diet and exercise alone or combined with metformin, sulfonylurea, or thiazolidinedione monotherapy or a combination of these drugs was evaluated in poorly controlled patients with type 2 diabetes (T2D) who were ineligible for participation in a placebo-controlled study (FREEDOM-1) because of severe hyperglycemia (HbA1c >10% [86 mmol/mol]). RESEARCH DESIGN AND METHODS This 39-week, open-label, phase 3 trial enrolled patients aged 18–80 years with HbA1c >10% to ≤12% (86–108 mmol/mol) and BMI 25–45 kg/m2. Patients received ITCA 650 20 μg/day for 13 weeks, then 60 μg/day for 26 weeks. The primary end point was change in HbA1c at week 39. RESULTS Sixty patients were enrolled. At baseline, mean HbA1c was 10.8% (94.7 mmol/mol) and mean (± SD) duration of diabetes was 8.6 (± 5.3) years. At week 39, there was a mean reduction in HbA1c of −2.8% (−30.3 mmol/mol; P < 0.001 vs. baseline) and in body weight of −1.2 kg ( P = 0.105), and 25% of patients achieved HbA1c <7% (53 mmol/mol). A reduction in HbA1c of ≥1% (≥10.9 mmol/mol) occurred in 90% of patients. The most common adverse events were nausea, vomiting, diarrhea, and headache. Gastrointestinal adverse events were generally transient and subsided over time; only 4 patients (6.7%) discontinued for gastrointestinal events. CONCLUSIONS Treatment with ITCA 650, the first injection-free glucagon-like peptide 1 receptor agonist, resulted in significant improvements in glycemic control in poorly controlled long-standing T2D patients with a high baseline HbA1c >10%.

中文翻译：

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新型药物装置GLP-1受体激动剂ITCA 650在不受控制的2型糖尿病和高基线HbA _1c中的临床影响：FREEDOM-1 HBL（高基线）研究

目标ITCA 650是一种皮下渗透微型泵，可连续皮下输送艾塞那肽3-6个月。在饮食控制不佳的2型糖尿病（T2D）患者中评估了ITCA 650的饮食，运动或单独饮食或与二甲双胍，磺酰脲或噻唑烷二酮单一疗法或这些药物联合使用的有效性，安全性和耐受性在安慰剂对照研究（FREEDOM-1）中，由于严重的高血糖症（HbA1c> 10％[86 mmol / mol]）。研究设计和方法这项为期39周，开放标签的3期试验招募了18-80岁，HbA1c> 10％至≤12％（86-108 mmol / mol）和BMI 25-45 kg / m2的患者。患者接受ITCA 650 20μg/天，持续13周，然后接受60μg/天，持续26周。主要终点是第39周时HbA1c的变化。结果纳入患者60例。在基线时，平均HbA1c为10.8％（94.7 mmol / mol），糖尿病的平均（±SD）病程为8.6（±5.3）年。在第39周时，HbA1c平均降低-2.8％（-30.3 mmol / mol；相对于基线，P <0.001）和体重-1.2 kg（P = 0.105），并且25％的患者达到了HbA1c <7％（53 mmol / mol）。90％的患者HbA1c降低≥1％（≥10.9mmol / mol）。最常见的不良事件是恶心，呕吐，腹泻和头痛。胃肠道不良事件通常是暂时性的，并随着时间而消退。仅4例（6.7％）因胃肠道事件而中断。结论使用首个免注射胰高血糖素样肽1受体激动剂ITCA 650进行治疗，