Randomized trial of continuous subcutaneous delivery of exenatide by ITCA 650 versus twice-daily exenatide injections in metformin-treated type 2 diabetes.
Randomized trial of continuous subcutaneous delivery of exenatide by ITCA 650 versus twice-daily exenatide injections in metformin-treated type 2 diabetes.
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DOI：
10.2337/dc12-2410
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发表时间：
2013-09
期刊：
影响因子：
16.2
通讯作者：
Baron MA
中科院分区：
文献类型：
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作者：
Henry RR;Rosenstock J;Logan DK;Alessi TR;Luskey K;Baron MA
在2型糖尿病受试者中评价ITCA 650（艾塞那肽连续皮下微型渗透泵给药系统）与每日两次艾塞那肽注射（Ex-BID）的比较。我们在二甲双胍控制不佳的2型糖尿病患者中进行了一项随机、两阶段、24周、开放标签、2期研究。第I阶段：155例受试者随机接受20或40 μg/天ITCA 650或Ex-BID 5→10 μg。第II阶段：131例受试者被重新随机分配至20、40、60或80 μg/天ITCA 650组。在第12周和第24周评价HbA 1c、体重和空腹血糖较基线的变化。12周和24周后，所有组的HbA 1c均显著降低。第一阶段：20和40 μg/天ITCA 650组和Ex-BID组HbA 1c相对于平均基线7.9-8.0%的平均变化分别为-0.98、-0.95和-0.72%，分别有63、65和50%的受试者达到HbA 1c水平≤7%（P < 0.05）。第二阶段：60和80 μg/天ITCA 650组HbA 1c显著（P < 0.05）降低（较基线降低1.4%），第24周时分别有86%和78%的受试者达到HbA 1c ≤7%。除20→20 μg/d组外，其余各组体重均下降2.8- 3.7kg（P < 0.05）。ITCA 650的耐受性良好;与Ex-BID相比，20 μg/天剂量组的恶心较低且为一过性; 60 μg/天剂量组的耐受性和HbA 1c降低最佳。ITCA 650显著降低HbA 1c和体重，耐受性良好。认为20→60 μg/天方案是III期进一步检查的最佳剂量。
To evaluate ITCA 650, a continuous subcutaneous miniature osmotic pump delivery system of exenatide versus twice-daily exenatide injections (Ex-BID) in subjects with type 2 diabetes. We conducted a randomized, two-stage, 24-week, open-label, phase 2 study in type 2 diabetes inadequately controlled with metformin. Stage I: 155 subjects were randomized to 20 or 40 μg/day of ITCA 650 or Ex-BID 5→10 μg. Stage II: 131 subjects were rerandomized to 20, 40, 60, or 80 μg/day of ITCA 650. Change from baseline for HbA1c, weight, and fasting plasma glucose were evaluated at weeks 12 and 24. HbA1c was significantly lower in all groups after 12 and 24 weeks. Stage I: mean change in HbA1c from a mean baseline of 7.9–8.0% was −0.98, −0.95, and −0.72% for the 20 and 40 μg/day ITCA 650 and Ex-BID groups, respectively, with 63, 65, and 50% of subjects achieving HbA1c levels ≤7% (P < 0.05). Stage II: significant (P < 0.05) reductions in HbA1c (∼1.4% from baseline) were achieved with 60 and 80 μg/day ITCA 650, and 86 and 78% of subjects achieved HbA1c ≤7% at 24 weeks; respectively. Weight was reduced by 2.8–3.7 kg (P < 0.05) at 24 weeks in all except the 20→20 μg/day group. ITCA 650 was well tolerated; nausea was lower and transient with 20 μg/day relative to Ex-BID; and 60 μg/day had the best profile of tolerability and HbA1c lowering. ITCA 650 significantly reduced HbA1c and weight and was well tolerated. The 20→60 μg/day regimen was considered the best dose for further examination in phase 3.