胰高血糖素样肽-1和二甲双胍治疗2型糖尿病的叠加降糖效应

1.       Additive Glucose-Lowering Effects of Glucagon-Like Peptide-1 and Metformin in Type 2 Diabetes

胰高血糖素样肽-1和二甲双胍治疗2型糖尿病的叠加降糖效应海南医学院第一附属医院内分泌科王新军

OBJECTIVE—The incretin hormone glucagon-like peptide-1 (GLP-1) reduces plasma glucose in type 2 diabetic patients by stimulating insulin secretion and inhibiting glucagon secretion. The biguanide metformin is believed to lower plasma glucose without affecting insulin secretion. We conducted this study to investigate the effect of a combination therapy with GLP-1 and metformin, which could theoretically be additive, in type 2 diabetic patients.

目的：肠促胰素胰高血糖素样肽-1（GLP - 1）通过刺激胰岛素分泌和抑制胰高血糖素分泌降低2型糖尿病患者血浆葡萄糖。目前认为双胍类药物二甲双胍降低血糖但不不影响胰岛素分泌。我们进行这项研究，以观察GLP - 1和二甲双胍联合治疗的效果，在2型糖尿病患者理论上是联合治疗具有叠加效果。

RESEARCH DESIGN AND METHODS—In a semiblinded randomized crossover study, seven patients received treatment with metformin (1,500 mg daily orally) alternating with GLP-1 (continuous subcutaneous infusion of 2.4 pmol · kg–1 · min–1) alternating with a combination of metformin and GLP-1 for 48 h. Under fixed energy intake, we examined the effects on plasma glucose, insulin, C-peptide, glucagon, and appetite.

研究设计和方法：在半双盲随机交叉研究中，7名患者接受二甲双胍治疗（每日1500mg口服）然后进行GLP – 1治疗（持续皮下输注2.4 pmol · kg–1 · min–1），最后转为二甲双胍和GLP - 1 联合治疗48小时。在固定能量摄入的情况下，我们检查了药物对血糖、胰岛素、C肽、胰高血糖素和食欲的效果。

RESULTS—Fasting plasma glucose (day 2) decreased from 13.9 ± 1 (no treatment) to 11.2 ± 0.4 (metformin) and 11.5 ± 0.5 (GLP-1) and further decreased to 9.4 ± 0.7 (combination therapy) (P = 0.0005, no difference between monotherapy with GLP-1 and metformin). The 24-h mean plasma glucose (day 2) decreased from 11.8 ± 0.5 (metformin) and 11.7 ± 0.8 (GLP-1) to 9.8 ± 0.5 (combination) (P = 0.02, no difference between GLP-1 and metformin). Insulin levels were similar between the three regimens, but glucagon levels were significantly reduced with GLP-1 compared with metformin (P = 0.0003). Combination therapy had no additional effect on appetite scores.

结果：空腹血糖（第2天）从13.9± 1（未治疗）下降到11.2 ± 0.4（二甲双胍）和11.5 ± 0.5（GLP - 1），并进一步下降至9.4 ± 0.7（联合治疗）（P = 0.0005，GLP - 1和二甲双胍单药治疗之间没有差异）。 24小时平均血浆葡萄糖（第2天）从11.8 ± 0.5（二甲双胍）和11.7 ± 0.8（GLP - 1）下降为9.8 ± 0.5（组合）（P = 0.02， GLP - 1和二甲双胍之间没有差异）。三个方案胰岛素水平之间类似，与二甲双胍相比，GLP - 1胰高血糖素水平显着减少（P = 0.0003）。联合治疗没有对食欲积分产生额外效果。