Trischitta V, Italia S, Raimondo M, Guardabasso V, Licciardello C, Runello F, Mazzarino S, Sangiorgi L, Anello M, Vigneri R
Divisione ed Unità di Ricerca di Endocrinologia, Istituto Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
J Endocrinol Invest. 1998 Dec;21(11):744-7. doi: 10.1007/BF03348039.
The treatment of NIDDM patients with secondary failure to sulphonylurea is a common problem. We performed a crossover study in 50 NIDDM patients with secondary failure to glibenclamide by comparing the addition to sulphonylurea of either a low-dose bedtime NPH insulin or a t.i.d. oral metformin and by analyzing treatment efficacy in relation to patient and disease characteristics. Both combined therapies clearly improved glycaemic control. HbA1 c were similarly reduced by the addition of either bedtime NPH insulin (7.6+/-0.34 vs 8.7+/-0.35, p<0.01) or metformin (7.6+/-0.22 vs 8.6+/-0.31, p<0.01). Also fasting plasma glucose (FPG) and post-prandial plasma glucose (PPPG) significantly decreased (p<0.01) with both treatments. Bed-time NPH insulin was more effective on FPG reduction than metformin (-36+/-2% vs -25+/-2%, p<0.01); in contrast, metformin addition was more effective on PPPG reduction than bedtime NPH insulin addition (-30+/-2% vs 20+/-3%, p<0.01). Serum cholesterol was marginally but significantly decreased after metformin (5.49+/-0.19 vs 5.91 +/-0.18 mM, p<0.05) but not after NPH insulin. Body weight increase was significantly greater after insulin addition than after metformin (1.47+/-0.25 Kg vs 0.64+/-0.17 p=0.02). All patients preferred the addition of metformin rather than NPH insulin. None of the measured clinical and metabolic variables (before treatment FPG and PPPG, HbA1 c, post-glucagon C-peptide levels, insulin sensitivity, patient age, BMI and diabetes duration) significantly correlated to the efficacy of the two combined treatments studied. In conclusion, in NIDDM patients with secondary failure to sulphonylureas the addition of either low-dose bedtime NPH insulin or t.i.d. metformin is similarly effective in improving glycaemic control. Metformin is better accepted by patients and provides a modest advantage in terms of body weight and cholesterol levels. The most common clinical and metabolic variables are not useful for predicting the efficacy of these two combined treatments.
对磺脲类药物继发失效的非胰岛素依赖型糖尿病（NIDDM）患者进行治疗是一个常见问题。我们对50例对格列本脲继发失效的NIDDM患者进行了一项交叉研究，比较在磺脲类药物基础上加用低剂量睡前中效胰岛素（NPH）或每日三次口服二甲双胍，并分析治疗效果与患者及疾病特征的关系。两种联合治疗均明显改善了血糖控制。加用睡前NPH胰岛素（糖化血红蛋白[HbA1c]从8.7±0.35降至7.6±0.34，p<0.01）或二甲双胍（HbA1c从8.6±0.31降至7.6±0.22，p<0.01）后，HbA1c均有类似程度的降低。两种治疗方法均使空腹血糖（FPG）和餐后血糖（PPPG）显著下降（p<0.01）。睡前NPH胰岛素在降低FPG方面比二甲双胍更有效（分别降低-36±2%和-25±2%，p<0.01）；相反，加用二甲双胍在降低PPPG方面比加用睡前NPH胰岛素更有效（分别降低-30±2%和-20±3%，p<0.01）。加用二甲双胍后血清胆固醇略有但显著下降（从5.91±0.18 mM降至5.49±0.19 mM，p<0.05），而加用NPH胰岛素后则无此变化。加用胰岛素后体重增加明显大于加用二甲双胍后（分别增加1.47±0.25 kg和0.64±0.17 kg，p=0.02）。所有患者更倾向于加用二甲双胍而非NPH胰岛素。所测量的临床和代谢变量（治疗前FPG和PPPG、HbA1c、胰高血糖素后C肽水平、胰岛素敏感性、患者年龄、体重指数[BMI]和糖尿病病程）均与所研究的两种联合治疗的疗效无显著相关性。总之，对于对磺脲类药物继发失效的NIDDM患者，加用低剂量睡前NPH胰岛素或每日三次二甲双胍在改善血糖控制方面同样有效。二甲双胍更易被患者接受，且在体重和胆固醇水平方面有一定优势。最常见的临床和代谢变量无助于预测这两种联合治疗的疗效。
