DeFronzo R A, Goodman A M
Diabetes Division, University of Texas Health Science Center, San Antonio, TX 78284, USA.
N Engl J Med. 1995 Aug 31;333(9):541-9. doi: 10.1056/NEJM199508313330902.
Sulfonylurea drugs have been the only oral therapy available for patients with non-insulin-dependent diabetes mellitus (NIDDM) in the United States. Recently, however, metformin has been approved for the treatment of NIDDM.
We performed two large, randomized, parallel-group, double-blind, controlled studies in which metformin or another treatment was given for 29 weeks to moderately obese patients with NIDDM whose diabetes was inadequately controlled by diet (protocol 1: metformin vs. placebo; 289 patients), or diet plus glyburide (protocol 2: metformin and glyburide vs. metformin vs. glyburide; 632 patients). To determine efficacy we measured plasma glucose (while the patients were fasting and after the oral administration of glucose), lactate, lipids, insulin, and glycosylated hemoglobin before, during, and at the end of the study.
In protocol 1, at the end of the study the 143 patients in the metformin group, as compared with the 146 patients in the placebo group, had lower mean (+/- SE) fasting plasma glucose concentrations (189 +/- 5 vs. 244 +/- 6 mg per deciliter [10.6 +/- 0.3 vs. 13.7 +/- 0.3 mmol per liter], P < 0.001) and glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.6 +/- 0.2 percent, P < 0.001). In protocol 2, the 213 patients given metformin and glyburide, as compared with the 210 patients treated with glyburide alone, had lower mean fasting plasma glucose concentrations (187 +/- 4 vs. 261 +/- 4 mg per deciliter [10.5 +/- 0.2 vs. 14.6 +/- 0.2 mmol per liter], P < 0.001) and glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.7 +/- 0.1 percent, P < 0.001). The effect of metformin alone was similar to that of glyburide alone. Eighteen percent of the patients given metformin and glyburide had symptoms compatible with hypoglycemia, as compared with 3 percent in the glyburide group and 2 percent in the metformin group. In both protocols the patients given metformin had statistically significant decreases in plasma total and low-density lipoprotein cholesterol and triglyceride concentrations, whereas the values in the respective control groups did not change. There were no significant changes in fasting plasma lactate concentrations in any of the groups.
Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone.
在美国，磺脲类药物一直是唯一可用于非胰岛素依赖型糖尿病（NIDDM）患者的口服治疗药物。然而，最近二甲双胍已被批准用于治疗NIDDM。
我们进行了两项大型、随机、平行组、双盲、对照研究，其中将二甲双胍或其他治疗方法给予中度肥胖的NIDDM患者29周，这些患者的糖尿病通过饮食控制不佳（方案1：二甲双胍与安慰剂对比；289例患者），或饮食加格列本脲（方案2：二甲双胍和格列本脲对比二甲双胍对比格列本脲；632例患者）。为了确定疗效，我们在研究前、研究期间和研究结束时测量了血浆葡萄糖（患者空腹时以及口服葡萄糖后）、乳酸、血脂、胰岛素和糖化血红蛋白。
在方案1中，研究结束时，二甲双胍组的143例患者与安慰剂组的146例患者相比，空腹血浆葡萄糖平均（±标准误）浓度更低（189±5 vs. 244±6mg/分升[10.6±0.3 vs. 13.7±0.3mmol/升]，P<0.001），糖化血红蛋白值也更低（7.1±0.1% vs. 8.6±０.2%，P<0.001）。在方案2中，接受二甲双胍和格列本脲治疗的213例患者与仅接受格列本脲治疗的210例患者相比，空腹血浆葡萄糖平均浓度更低（187±4 vs. 261±4mg/分升[10.5±0.2 vs. 14.6±0.2mmol/升]，P<0.001），糖化血红蛋白值也更低（7.1±0.1% vs. 8.7±0.1%，P<0.001）。单独使用二甲双胍的效果与单独使用格列本脲的效果相似。接受二甲双胍和格列本脲治疗的患者中有18%出现与低血糖相符的症状，而格列本脲组为3%，二甲双胍组为2%。在两个方案中，接受二甲双胍治疗的患者血浆总胆固醇、低密度脂蛋白胆固醇和甘油三酯浓度均有统计学意义的下降，而各自对照组的值没有变化。任何组的空腹血浆乳酸浓度均无显著变化。
二甲双胍单药治疗以及二甲双胍与磺脲类药物联合治疗耐受性良好，可改善饮食或单独使用磺脲类药物治疗效果不佳的NIDDM患者的血糖控制和血脂浓度。
