与新型长效胰岛素 LY2605541 和甘精胰岛素相比，尽管在 1 型和 2 型糖尿病中都能改善血糖控制，但体重变化却截然不同。

Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite similar improved glycaemic control in T1DM and T2DM.

出版信息

Diabetes Obes Metab. 2014 Apr;16(4):351-6. doi: 10.1111/dom.12223.

PMID:24719911

Abstract

AIMS

The basal insulin analogue LY2605541, a PEGylated insulin lispro with prolonged duration of action, was previously shown to be associated with modest weight loss in Phase 2, randomized, open-label trials in type 2 (N=288) and type 1 (N=137) diabetes mellitus (T2DM and T1DM), compared with modest weight gain with insulin glargine. Exploratory analyses were conducted to further characterize these findings.

METHODS

Pearson correlations between change in body weight and other variables were calculated. Continuous variables were analysed using a mixed linear model with repeated measurements. Proportions of subjects with weight loss were analysed using Fisher's exact test for T2DM and Nagelkerke's method for T1DM.

RESULTS

Weight loss was more common in LY2605541-treated patients than in patients treated with insulin glargine (T2DM: 56.9 vs. 40.2%, p=0.011; T1DM: 66.1 vs. 40.3%, p<0.001). More LY2605541-treated patients experienced ≥5% weight loss compared to patients treated with glargine (T2DM: 4.8 vs. 0%, p=0.033; T1DM: 11.9 vs. 0.8%, p<0.001). In both the T1DM and T2DM studies, weight change did not correlate with baseline body mass index (BMI), or change in HDL-cholesterol in either treatment group. No consistent correlations were found across both studies between weight change and any of the variables assessed; however, weight change was significantly correlated with hypoglycaemia rate in glargine-treated T2DM patients.

CONCLUSION

In two Phase 2 trials, improved glycaemic control with long-acting basal insulin analogue LY2605541 is associated with weight loss in previously insulin-treated patients. This weight change is independent of baseline BMI or hypoglycaemia.

摘要

目的

先前的 2 期、随机、开放标签临床试验表明，基础胰岛素类似物 LY2605541（一种作用持续时间延长的聚乙二醇化胰岛素赖脯肽）与 2 型（N=288）和 1 型（N=137）糖尿病患者的体重适度减轻相关，而甘精胰岛素则与体重适度增加相关。进行了探索性分析以进一步阐明这些发现。

方法

计算体重变化与其他变量之间的 Pearson 相关性。使用具有重复测量的混合线性模型分析连续变量。使用 Fisher 确切检验分析 T2DM 中体重减轻的受试者比例，使用 Nagelkerke 方法分析 T1DM 中体重减轻的受试者比例。

结果

与接受甘精胰岛素治疗的患者相比，接受 LY2605541 治疗的患者体重减轻更为常见（T2DM：56.9% vs. 40.2%，p=0.011；T1DM：66.1% vs. 40.3%，p<0.001）。与接受甘精胰岛素治疗的患者相比，接受 LY2605541 治疗的患者中有更多患者出现体重减轻≥5%（T2DM：4.8% vs. 0%，p=0.033；T1DM：11.9% vs. 0.8%，p<0.001）。在 T1DM 和 T2DM 研究中，体重变化与基线体重指数（BMI）或两组中任何治疗组的高密度脂蛋白胆固醇（HDL-cholesterol）变化均无相关性。在两项研究中，体重变化与评估的任何变量之间均未发现一致的相关性；然而，在接受甘精胰岛素治疗的 T2DM 患者中，体重变化与低血糖发生率显著相关。