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利拉鲁肽治疗 2 型糖尿病,作为单药治疗或与二甲双胍联合治疗,每日一次的人胰高血糖素样肽-1 类似物,可减轻体重,主要是由于脂肪组织减少。

Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue.

机构信息

Faculty of Health Science, Orebro University, Orebro, Sweden.

出版信息

Diabetes Obes Metab. 2009 Dec;11(12):1163-72. doi: 10.1111/j.1463-1326.2009.01158.x.

Abstract

AIM

The effect on body composition of liraglutide, a once-daily human glucagon-like peptide-1 analogue, as monotherapy or added to metformin was examined in patients with type 2 diabetes (T2D).

METHODS

These were randomized, double-blind, parallel-group trials of 26 [Liraglutide Effect and Action in Diabetes-2 (LEAD-2)] and 52 weeks (LEAD-3). Patients with T2D, aged 18-80 years, body mass index (BMI) < or =40 kg/m(2) (LEAD-2), < or =45 kg/m(2) (LEAD-3) and HbA1c 7.0-11.0% were included. Patients were randomized to liraglutide 1.8, 1.2 or 0.6 mg/day, placebo or glimepiride 4 mg/day, all combined with metformin 1.5-2 g/day in LEAD-2 and to liraglutide 1.8, 1.2 or glimepiride 8 mg/day in LEAD-3. LEAD-2/3: total lean body tissue, fat tissue and fat percentage were measured. LEAD-2: adipose tissue area and hepatic steatosis were assessed.

RESULTS

LEAD-2: fat percentage with liraglutide 1.2 and 1.8 mg/metformin was significantly reduced vs. glimepiride/metformin (p < 0.05) but not vs. placebo. Visceral and subcutaneous adipose tissue areas were reduced from baseline in all liraglutide/metformin arms. Except with liraglutide 0.6 mg/metformin, reductions were significantly different vs. changes seen with glimepiride (p < 0.05) but not with placebo. Liver-to-spleen attenuation ratio increased with liraglutide 1.8 mg/metformin possibly indicating reduced hepatic steatosis. LEAD-3: reductions in fat mass and fat percentage with liraglutide monotherapy were significantly different vs. increases with glimepiride (p < 0.01).

CONCLUSION

Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D.

摘要

目的

以每日一次的人胰高血糖素样肽-1 类似物利拉鲁肽作为单一疗法或与二甲双胍联合应用,观察其对 2 型糖尿病(T2D)患者的身体成分的影响。

方法

这是两项随机、双盲、平行分组试验,分别持续 26 周(LEAD-2)和 52 周(LEAD-3)。纳入的患者为 T2D 患者,年龄 18-80 岁,体重指数(BMI)<或=40 kg/m(2)(LEAD-2),<或=45 kg/m(2)(LEAD-3),糖化血红蛋白(HbA1c)7.0-11.0%。患者被随机分配至利拉鲁肽 1.8、1.2 或 0.6 mg/天、安慰剂或格列美脲 4 mg/天,所有这些治疗方案均与二甲双胍 1.5-2 g/天联合应用,在 LEAD-2 中还联合应用利拉鲁肽 1.8、1.2 或格列美脲 8 mg/天。LEAD-2/3:测量总瘦体组织、脂肪组织和脂肪百分比。LEAD-2:评估脂肪组织面积和肝脂肪变性。

结果

LEAD-2:与格列美脲/二甲双胍相比,利拉鲁肽 1.2 和 1.8 mg/二甲双胍可显著降低脂肪百分比(p < 0.05),但与安慰剂相比无差异。所有利拉鲁肽/二甲双胍组的内脏和皮下脂肪组织面积均较基线减少。除了利拉鲁肽 0.6 mg/二甲双胍,与格列美脲相比,这些变化有显著差异(p < 0.05),但与安慰剂相比无差异。利拉鲁肽 1.8 mg/二甲双胍治疗后肝脾衰减比增加,可能表明肝脂肪变性减少。LEAD-3:利拉鲁肽单药治疗时体脂质量和脂肪百分比的降低与格列美脲的增加有显著差异(p < 0.01)。

结论

在 T2D 患者中,与格列美脲相比,利拉鲁肽(单药或与二甲双胍联合应用)可显著降低体脂质量和脂肪百分比。

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