利拉鲁肽，一种每日一次的人胰高血糖素样肽-1类似物，在26周内添加到磺脲类药物中，与在2型糖尿病患者中添加罗格列酮或安慰剂相比，在血糖和体重控制方面产生了更大的改善（LEAD-1 SU）。

Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU).

作者信息

Marre M, Shaw J, Brändle M, Bebakar W M W, Kamaruddin N A, Strand J, Zdravkovic M, Le Thi T D, Colagiuri S

机构信息

Service d'Endocrinologie Diabétologie Nutrition, Groupe Hospitalier Bichat-Claude Bernard, Paris, France.

出版信息

Diabet Med. 2009 Mar;26(3):268-78. doi: 10.1111/j.1464-5491.2009.02666.x.

AIM

To compare the effects of combining liraglutide (0.6, 1.2 or 1.8 mg/day) or rosiglitazone 4 mg/day (all n >or= 228) or placebo (n = 114) with glimepiride (2-4 mg/day) on glycaemic control, body weight and safety in Type 2 diabetes.

METHODS

In total, 1041 adults (mean +/- sd), age 56 +/- 10 years, weight 82 +/- 17 kg and glycated haemoglobin (HbA(1c)) 8.4 +/- 1.0% at 116 sites in 21 countries were stratified based on previous oral glucose-lowering mono : combination therapies (30 : 70%) to participate in a five-arm, 26-week, double-dummy, randomized study.

RESULTS

Liraglutide (1.2 or 1.8 mg) produced greater reductions in HbA(1c) from baseline, (-1.1%, baseline 8.5%) compared with placebo (+0.2%, P < 0.0001, baseline 8.4%) or rosiglitazone (-0.4%, P < 0.0001, baseline 8.4%) when added to glimepiride. Liraglutide 0.6 mg was less effective (-0.6%, baseline 8.4%). Fasting plasma glucose decreased by week 2, with a 1.6 mmol/l decrease from baseline at week 26 with liraglutide 1.2 mg (baseline 9.8 mmol/l) or 1.8 mg (baseline 9.7 mmol/l) compared with a 0.9 mmol/l increase (placebo, P < 0.0001, baseline 9.5 mmol/l) or 1.0 mmol/l decrease (rosiglitazone, P < 0.006, baseline 9.9 mmol/l). Decreases in postprandial plasma glucose from baseline were greater with liraglutide 1.2 or 1.8 mg [-2.5 to -2.7 mmol/l (baseline 12.9 mmol/l for both)] compared with placebo (-0.4 mmol/l, P < 0.0001, baseline 12.7 mmol/l) or rosiglitazone (-1.8 mmol/l, P < 0.05, baseline 13.0 mmol/l). Changes in body weight with liraglutide 1.8 mg (-0.2 kg, baseline 83.0 kg), 1.2 mg (+0.3 kg, baseline 80.0 kg) or placebo (-0.1 kg, baseline 81.9 kg) were less than with rosiglitazone (+2.1 kg, P < 0.0001, baseline 80.6 kg). Main adverse events for all treatments were minor hypoglycaemia (< 10%), nausea (< 11%), vomiting (< 5%) and diarrhoea (< 8%).

CONCLUSIONS

Liraglutide added to glimepiride was well tolerated and provided improved glycaemic control and favourable weight profile.

目的

比较利拉鲁肽（0.6、1.2或1.8毫克/天）或罗格列酮4毫克/天（所有n≥228）或安慰剂（n = 114）与格列美脲（2 - 4毫克/天）联合使用对2型糖尿病患者血糖控制、体重及安全性的影响。

方法

在21个国家的116个研究点，共有1041名成年人（平均±标准差）参与研究，年龄56±10岁，体重82±17千克，糖化血红蛋白（HbA1c）为8.4±1.0%。根据既往口服降糖单药治疗与联合治疗的比例（30 : 70%）进行分层，参与一项五组、为期26周的双盲、随机研究。

结果

与安慰剂（+0.2%，P < 0.0001，基线8.4%）或罗格列酮（-0.4%，P < 0.0001，基线8.4%）相比，利拉鲁肽（1.2或1.8毫克）联合格列美脲时，HbA1c从基线水平的降低幅度更大（-1.1%，基线8.5%）。利拉鲁肽0.6毫克的效果较差（-0.6%，基线8.4%）。空腹血糖在第2周开始下降，第26周时，利拉鲁肽1.2毫克（基线9.8毫摩尔/升）或1.8毫克（基线9.7毫摩尔/升）组空腹血糖较基线下降1.6毫摩尔/升，而安慰剂组上升0.9毫摩尔/升（P < 0.0001，基线9.5毫摩尔/升），罗格列酮组下降1.0毫摩尔/升（P < 0.006，基线9.9毫摩尔/升）。与安慰剂（-0.4毫摩尔/升，P < 0.0001，基线12.7毫摩尔/升）或罗格列酮（-1.8毫摩尔/升，P < 0.05，基线13.0毫摩尔/升）相比，利拉鲁肽1.2或1.8毫克组餐后血糖较基线的下降幅度更大[-2.5至-2.7毫摩尔/升（两者基线均为12.9毫摩尔/升）]。利拉鲁肽1.8毫克（-0.2千克，基线83.0千克）、1.2毫克（+0.3千克，基线80.0千克）或安慰剂（-0.1千克，基线81.9千克）组的体重变化小于罗格列酮组（+2.1千克，P < 0.0001，基线80.6千克）。所有治疗的主要不良事件为轻度低血糖（< 10%）、恶心（< 11%）、呕吐（< 5%）和腹泻（< 8%）。