Better Glycemic Control and Weight Loss With the Novel Long-Acting Basal Insulin LY2605541 Compared With Insulin Glargine in Type 1 Diabetes
Better Glycemic Control and Weight Loss With the Novel Long-Acting Basal Insulin LY2605541 Compared With Insulin Glargine in Type 1 Diabetes
复制标题
与甘精胰岛素相比，新型长效基础胰岛素 LY2605541 在 1 型糖尿病中具有更好的血糖控制和减肥效果
作者：
J. Rosenstock;R. Bergenstal;T. Blevins;L. Morrow;M. Prince;Y. Qu;V. Sinha;D. Howey;S. Jacober
目的比较LY2605541与甘精胰岛素作为基础给药方案治疗1型糖尿病对日平均血糖的影响。研究设计与方法在这项随机的2期开放标签2×2交叉试验中，137名患者每天接受一次基础胰岛素(LY2605541或甘精)加餐时胰岛素治疗8周，然后交叉治疗8周。每日平均血糖从8点自我监测的血糖谱中获得。非劣性边际为10.8 mg/dL。结果与甘精胰岛素相比，LY2605541的日平均血糖符合非劣势和优势标准(144.2比151.7 mg/dL，最小二乘均值差=−9.9 mg/dL[90%CI−14.6to−5.2]，P<；0.001)。与甘精胰岛素相比，服用LY2605541可降低空腹血糖变异性和糖化血红蛋白(P<；0.001)。LY2605541组餐时胰岛素用量减少，甘精胰岛素组餐时胰岛素用量增加。平均体重下降1.2kgLY2605541和增加0.7kg甘精胰岛素(P<；0.001)。与甘精胰岛素相比，LY2605541的总低血糖发生率较高(P=0.04)，夜间低血糖发生率较低(P=0.01)。不良反应(包括严重低血糖)相似，尽管LY2605541出现更多与胃肠道相关的事件(15%比4%，P<；0.001)。与甘精胰岛素相比，LY2605541的丙氨酸氨基转移酶、天冬氨酸氨基转移酶、甘油三酯和低密度脂蛋白胆固醇的平均变化(均在正常范围内)较高，而高密度脂蛋白-胆固醇的平均变化较低(均P<；0.02)。结论在1型糖尿病患者中，与甘精胰岛素相比，新型长效基础胰岛素LY2605541在血糖控制方面有更大的改善，总低血糖增加，夜间低血糖减少，体重减轻，餐时胰岛素用量减少。
OBJECTIVE To compare effects of LY2605541 versus insulin glargine on daily mean blood glucose as part of a basal-bolus regimen for type 1 diabetes. RESEARCH DESIGN AND METHODS In this randomized, Phase 2, open-label, 2 × 2 crossover study, 137 patients received once-daily basal insulin (LY2605541 or glargine) plus mealtime insulin for 8 weeks, followed by crossover treatment for 8 weeks. Daily mean blood glucose was obtained from 8-point self-monitored blood glucose profiles. The noninferiority margin was 10.8 mg/dL. RESULTS LY2605541 met noninferiority and superiority criteria compared with insulin glargine in daily mean blood glucose (144.2 vs. 151.7 mg/dL, least squares mean difference = −9.9 mg/dL [90% CI −14.6 to −5.2], P < 0.001). Fasting blood glucose variability and A1C were reduced with LY2605541 compared with insulin glargine (both P < 0.001). Mealtime insulin dose decreased with LY2605541 and increased with insulin glargine. Mean weight decreased 1.2 kg with LY2605541 and increased 0.7 kg with insulin glargine (P < 0.001). The total hypoglycemia rate was higher for LY2605541 (P = 0.04) and the nocturnal hypoglycemia rate was lower (P = 0.01), compared with insulin glargine. Adverse events (including severe hypoglycemia) were similar, although more gastrointestinal-related events occurred with LY2605541 (15% vs. 4%, P < 0.001). Mean changes (all within normal range) were higher for alanine aminotransferase, aspartate aminotransferase, triglycerides, and LDL-cholesterol and lower for HDL-cholesterol with LY2605541 compared with insulin glargine (all P < 0.02). CONCLUSIONS In type 1 diabetes, compared with insulin glargine, LY2605541, a novel, long-acting basal insulin, demonstrated greater improvements in glycemic control, increased total hypoglycemia, and reduced nocturnal hypoglycemia, as well as reduced weight and lowered mealtime insulin doses.