Diabetes Care. 1998 Jan;21(1):87-92. doi: 10.2337/diacare.21.1.87.
To assess the efficacy over 3 years of the addition of metformin to maximum sulfonylurea therapy in type 2 diabetes.
This multicenter randomized open-controlled trial was conducted in outpatient diabetes clinics in 15 U.K. hospitals. A total of 591 subjects who had already been randomly allocated to sulfonylurea therapy were taking maximum doses with suboptimal glycemic control, i.e., raised fasting plasma glucose (FPG) concentrations of 6-15 mmol/l but no significant hyperglycemic symptoms. The main outcome measures included FPG, glycated hemoglobin, protocol-defined marked hyperglycemia, body weight, blood pressure, fasting plasma lipids, compliance, and hypoglycemia and other side effects.
After the addition of metformin, FPG concentrations decreased by mean (95% CI) -0.47 (-0.82 to -0.13) mmol/l over 3 years compared with an increase of 0.44 (0.07-0.81) mmol/l in subjects on sulfonylurea alone (P < 0.00001). Median FPG concentrations at 3 years were 8.6 vs. 9.9 mmol/l, respectively (P < 0.00001), and HbA1c values were 7.5 and 8.1%, respectively (P = 0.006). Adjustment for baseline BMI or FPG concentration did not affect response to therapy. Only 7% of those allocated to sulfonylurea plus metformin developed protocol-defined marked hyperglycemia compared with 36% of those allocated to sulfonylurea alone (P < 0.0001). Fasting plasma lipids, body weight, and blood pressure did not change significantly. The incidence of hypoglycemic episodes did not differ between groups: 4% on sulfonylurea plus metformin and 2% on sulfonylurea alone (NS).
Early addition of metformin improved glycemic control in patients with suboptimal glycemic control while taking maximum sulfonylurea therapy, irrespective of obesity or baseline FPG concentrations.
评估在2型糖尿病患者中，在最大剂量磺脲类药物治疗基础上加用二甲双胍3年的疗效。
这项多中心随机开放对照试验在英国15家医院的糖尿病门诊进行。共有591名已被随机分配接受磺脲类药物治疗的受试者，正在服用最大剂量但血糖控制欠佳，即空腹血糖（FPG）浓度升高至6 - 15 mmol/l且无明显高血糖症状。主要结局指标包括FPG、糖化血红蛋白、方案定义的显著高血糖、体重、血压、空腹血脂、依从性以及低血糖和其他副作用。
加用二甲双胍后，3年内FPG浓度平均（95%CI）下降了 - 0.47（ - 0.82至 - 0.13）mmol/l，而单纯接受磺脲类药物治疗的受试者FPG浓度升高了0.44（0.07 - 0.81）mmol/l（P < 0.00001）。3年时FPG浓度中位数分别为8.6和9.9 mmol/l（P < 0.00001），糖化血红蛋白值分别为7.5%和8.1%（P = 0.006）。对基线体重指数或FPG浓度进行调整并不影响治疗反应。分配接受磺脲类药物加二甲双胍治疗的患者中，只有7%发生了方案定义的显著高血糖，而单纯接受磺脲类药物治疗的患者中这一比例为36%（P < 0.0001）。空腹血脂、体重和血压无显著变化。两组低血糖发作的发生率无差异：磺脲类药物加二甲双胍组为4%，单纯磺脲类药物组为2%（无显著性差异）。
在接受最大剂量磺脲类药物治疗且血糖控制欠佳的患者中，早期加用二甲双胍可改善血糖控制，无论患者是否肥胖或基线FPG浓度如何。
