Lund University, Lund, Sweden.
Diabetes Care. 2013 Sep;36(9):2543-50. doi: 10.2337/dc12-2006. Epub 2013 Mar 27.
To examine the efficacy and safety of lixisenatide (20 μg once daily, administered before the morning or evening meal) as add-on therapy in patients with type 2 diabetes insufficiently controlled with metformin alone.
This was 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.
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.
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.
研究利西那肽（每日一次 20μg，于早餐或晚餐前给药）作为二甲双胍控制不佳的 2 型糖尿病患者的附加疗法的疗效和安全性。
这是一项为期 24 周、随机、双盲、安慰剂对照的研究，纳入了 680 例二甲双胍控制不佳的 2 型糖尿病患者（HbA1c 7-10%[53-86mmol/mol]）。患者随机接受利西那肽清晨（n=255）、利西那肽傍晚（n=255）、清晨安慰剂（n=85）或傍晚安慰剂（n=85）注射。
利西那肽清晨注射与联合安慰剂相比，显著降低了平均 HbA1c（平均变化-0.9%[9.8mmol/mol] vs.-0.4%[4.4mmol/mol]；与安慰剂相比，最小二乘（LS）均值差-0.5%[5.5mmol/mol]，P<0.0001）。利西那肽傍晚注射也显著降低了 HbA1c（平均变化-0.8%[8.7mmol/mol] vs.-0.4%[4.4mmol/mol]；LS 均值差-0.4%[4.4mmol/mol]，P<0.0001）。利西那肽清晨注射与清晨安慰剂相比，显著降低了餐后 2 小时血糖（平均变化-5.9 vs.-1.4mmol/L；LS 均值差-4.5mmol/L，P<0.0001）。两组患者的空腹血浆葡萄糖 LS 均值差均有显著差异（清晨组-0.9mmol/L，P<0.0001；傍晚组-0.6mmol/L，P=0.0046）。所有组的平均体重均有相似程度的下降。利西那肽组的不良反应发生率为 69.4%，安慰剂组为 60.0%。利西那肽清晨和傍晚组的恶心和呕吐发生率分别为 22.7%和 9.4%，21.2%和 13.3%，安慰剂组分别为 7.6%和 2.9%。利西那肽清晨、傍晚和安慰剂组分别有 6、13 和 1 例患者发生症状性低血糖，均无严重事件。
在二甲双胍控制不佳的 2 型糖尿病患者中，每日一次给予利西那肽 20μg，无论在早晨还是傍晚给药，均能显著改善血糖控制，具有明显的餐后作用，且耐受性良好。
