Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD).
Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD).
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DOI：
10.2337/dc08-2124
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发表时间：
2009-07
期刊：
影响因子：
16.2
通讯作者：
LEAD-4 Study Investigators
中科院分区：
文献类型：
--
作者：
Zinman B;Gerich J;Buse JB;Lewin A;Schwartz S;Raskin P;Hale PM;Zdravkovic M;Blonde L;LEAD-4 Study Investigators
确定利拉鲁肽（胰高血糖素样肽-1受体激动剂）与二甲双胍和罗格列酮联合治疗2型糖尿病的疗效和安全性。这项为期26周、双盲、安慰剂对照、平行组试验将533例受试者（1：1：1）随机分配至每日一次利拉鲁肽（1.2或1.8 mg）或利拉鲁肽安慰剂联合二甲双胍（1 g，每日两次）和罗格列酮（4 mg，每日两次）。受试者患有2型糖尿病，A1 C 7-11%（既往口服降糖药物[OAD]单药治疗≥3个月）或7-10%（既往OAD联合治疗≥3个月），BMI ≤45 kg/m2。与安慰剂组相比，利拉鲁肽组的平均A1 C值降低幅度显著更大（1.2和1.8 mg利拉鲁肽组的平均值± SE为−1.5 ± 0.1%，安慰剂组为−0.5 ± 0.1%）。1.2和1.8 mg组和安慰剂组空腹血糖分别降低40、44和8 mg/dl，餐后90分钟血糖分别降低47、49和14 mg/dl（所有利拉鲁肽组与安慰剂组相比P < 0.001）。与安慰剂组体重增加（0.6 ± 0.3 kg）相比，1.2和1.8 mg利拉鲁肽组出现剂量依赖性体重减轻（分别为1.0 ± 0.3和2.0 ± 0.3 kg）（P < 0.0001）。1.2和1.8 mg利拉鲁肽和安慰剂组的收缩压分别降低6.7、5.6和1.1 mmHg。与安慰剂相比，利拉鲁肽组的C肽和β细胞功能稳态模型评估显著增加，胰岛素原/胰岛素比值显著降低。利拉鲁肽组轻度低血糖发生率更高，但未发生严重低血糖。胃肠道不良事件在利拉鲁肽组更常见，但大多数发生在早期且为一过性。利拉鲁肽联合二甲双胍和噻唑烷二酮是一种耐受性良好的2型糖尿病联合治疗，可显著改善血糖控制。
To determine the efficacy and safety of liraglutide (a glucagon-like peptide-1 receptor agonist) when added to metformin and rosiglitazone in type 2 diabetes. This 26-week, double-blind, placebo-controlled, parallel-group trial randomized 533 subjects (1:1:1) to once-daily liraglutide (1.2 or 1.8 mg) or liraglutide placebo in combination with metformin (1 g twice daily) and rosiglitazone (4 mg twice daily). Subjects had type 2 diabetes, A1C 7–11% (previous oral antidiabetes drug [OAD] monotherapy ≥3 months) or 7–10% (previous OAD combination therapy ≥3 months), and BMI ≤45 kg/m2. Mean A1C values decreased significantly more in the liraglutide groups versus placebo (mean ± SE −1.5 ± 0.1% for both 1.2 and 1.8 mg liraglutide and −0.5 ± 0.1% for placebo). Fasting plasma glucose decreased by 40, 44, and 8 mg/dl for 1.2 and 1.8 mg and placebo, respectively, and 90-min postprandial glucose decreased by 47, 49, and 14 mg/dl, respectively (P < 0.001 for all liraglutide groups vs. placebo). Dose-dependent weight loss occurred with 1.2 and 1.8 mg liraglutide (1.0 ± 0.3 and 2.0 ± 0.3 kg, respectively) (P < 0.0001) compared with weight gain with placebo (0.6 ± 0.3 kg). Systolic blood pressure decreased by 6.7, 5.6, and 1.1 mmHg with 1.2 and 1.8 mg liraglutide and placebo, respectively. Significant increases in C-peptide and homeostasis model assessment of β-cell function and significant decreases in the proinsulin-to-insulin ratio occurred with liraglutide versus placebo. Minor hypoglycemia occurred more frequently with liraglutide, but there was no major hypoglycemia. Gastrointestinal adverse events were more common with liraglutide, but most occurred early and were transient. Liraglutide combined with metformin and a thiazolidinedione is a well-tolerated combination therapy for type 2 diabetes, providing significant improvements in glycemic control.
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影响因子：
7.3
作者：
Knudsen, LB;Nielsen, PF;Agerso, H
通讯作者：
Agerso, H
影响因子：
168.9
作者：
Turner, RC;Holman, RR;Ward, JD
通讯作者：
Ward, JD
影响因子：
39.2
作者：
Zinman, Bernard;Hoogwerf, Byron J.;Brodows, Robert G.
通讯作者：
Brodows, Robert G.
影响因子：
5.8
作者：
Gutzwiller, JP;Tschopp, S;Beglinger, C
通讯作者：
Beglinger, C
DOI：
10.1152/ajpendo.00237.2004
发表时间：
2004-12-01
影响因子：
5.1
作者：
Nyström, T;Gutniak, MK;Sjöholm, Å
通讯作者：
Sjöholm, Å