Diabetes Care：lixisenatide有效改善二甲双胍控制不佳的2型糖尿病人群的血糖

为了评价利西拉来(lixisenatide，每日1次20μg，早餐和晚餐前给药)辅助治疗二甲双胍控制不佳的2型糖尿病患者的有效性和安全性，来自瑞典隆德大学的Ahrén博士等人进行了一项研究，研究发现，利西拉来可显著改善二甲双胍控制不佳的2型糖尿病患者的血糖控制，且药物耐受性良好。研究结果在线发表于2013年3月27日美国的《糖尿病护理》(Diabetes Care)杂志上。
研究人员对680名二甲双胍控制不佳的2型糖尿病患者(HbA1c 7-10%[53-86mmol/mol])进行了一项为期24周、随机、双盲、安慰剂对照临床研究。患者随机分为利西拉来早上给药组(n=255)、利西拉来晚上给药组(n=255)、安慰剂早上给药组(n=85)和安慰剂晚上给药组(n=85)。
结果显示，与安慰剂早上和晚上给药组相比，利西拉来早上给药显著降低平均HbA1c含量(平均变化-0.9%[9.8mmol/mol] vs. -0.4%[4.4mmol/mol]; 两组间最小二乘[LS]平均差异-0.5%[5.5mmol/mol], P<0.001)。利西拉来晚上给药组HbA1c含量也显著降低(平均变化-0.8%[8.7mmol/mol] vs. -0.4% [4.4 mmol/mol]; LS平均差异-0.4%[4.4mmol/mol], P<0.0001)。与安慰剂早上给药组相比，利西拉来早上给药显著降低2h餐后血糖(平均变化-5.9 vs. -1.4mmol/L; LS平均差异-4.5mmol/L, P<0.0001)。与安慰剂组比较，利西拉来早上给药组和晚上给药组空腹血糖LS平均差异均具有显著性 (分别为-0.9mmol/L, P<0.0001；-0.6mmol/L, P=0.0046)。所有受试组平均体重降低程度相同。利西拉来给药组副反应发生率为69.4%，安慰剂组为60.0%。利西拉来早上给药组恶心和呕吐发生率分别为22.7%和9.4%，晚上给药组为21.2%和13.3%，而安慰剂组为7.6%和2.9%。利西拉来早上给药组、晚上给药组和安慰剂组各分别有6、13和1例患者出现症状性低血糖，没有严重偶发事件。
研究表明，对于二甲双胍控制不佳的2型糖尿病患者，每日1次20 μg(早上或晚上)利西拉来给药显著改善血糖控制，餐后给药效果明显，且药物耐受性良好。

 与糖尿病相关的拓展阅读：

• 2013 NIH 妊娠期糖尿病(GDM)诊断声明
• JAMA：褪黑激素分泌减少增加II型糖尿病风险
• DIABETES CARE：空腹血糖筛查妊娠糖尿病添新证
• Eur J Endocrinol: 1型糖尿病患者HbA1c水平过高能直接导致抑郁
• Diabetes Care：HbA1c水平的波动与糖尿病肾病有关
• GYNECOL ONCOL ：抗糖尿病药物与子宫内膜癌风险无关
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Efficacy and Safety of Lixisenatide Once-Daily Morning or Evening Injections in Type 2 Diabetes Inadequately Controlled on Metformin (GetGoal-M).
OBJECTIVE
Examine the efficacy and safety of lixisenatide (20 μg once daily, administered before the morning or evening meal) as add-on therapy in type 2 diabetes patients insufficiently controlled with metformin alone.
RESEARCH DESIGN AND METHODS
A 24-week, randomized, double-blind, placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes (HbA1c 7–10% [53−86 mmol/mol]). Patients were randomized to lixisenatide morning (n = 255), lixisenatide evening (n = 255), placebo morning (n = 85), or placebo evening (n = 85) injections.
RESULTS
Lixisenatide morning injection significantly reduced mean HbA1c versus combined placebo (mean change −0.9% [9.8 mmol/mol] vs. −0.4% [4.4 mmol/mol]; least squares [LS] mean difference vs. placebo −0.5% [5.5 mmol/mol], P < 0.0001). HbA1c was significantly reduced by lixisenatide evening injection (mean change –0.8% [8.7 mmol/mol] vs. –0.4% [4.4 mmol/mol]; LS mean difference –0.4% [4.4 mmol/mol], P < 0.0001). Lixisenatide morning injection significantly reduced 2-h postprandial glucose versus morning placebo (mean change −5.9 vs. −1.4 mmol/L; LS mean difference −4.5 mmol/L, P < 0.0001). LS mean difference in fasting plasma glucose was significant in both morning (–0.9 mmol/L, P < 0.0001) and evening (–0.6 mmol/L, P = 0.0046) groups versus placebo. Mean body weight decreased to a similar extent in all groups. Rates of adverse events were 69.4% in both lixisenatide groups and 60.0% in the placebo group. Rates for nausea and vomiting were 22.7 and 9.4% for lixisenatide morning and 21.2 and 13.3% for lixisenatide evening versus 7.6 and 2.9% for placebo, respectively. Symptomatic hypoglycemia occurred in 6, 13, and 1 patient for lixisenatide morning, evening, and placebo, respectively, with no severe episodes.
CONCLUSIONS
In patients with type 2 diabetes inadequately controlled on metformin, lixisenatide 20 μg once daily administered in the morning or evening significantly improved glycemic control, with a pronounced postprandial effect, and was well tolerated.