Katakami N, Yamasaki Y, Hayaishi-Okano R, Ohtoshi K, Kaneto H, Matsuhisa M, Kosugi K, Hori M
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.
Diabetologia. 2004 Nov;47(11):1906-13. doi: 10.1007/s00125-004-1547-8. Epub 2004 Nov 24.
AIM/HYPOTHESIS: Metformin is a well-known oral hypoglycaemic agent and has been commonly used, in combination with sulphonylurea, to treat type 2 diabetes. However, the advantageous effect of metformin plus sulphonylurea on diabetic macroangiopathy has yet to be clarified. To evaluate whether sulphonylurea or sulphonylurea plus metformin prevent diabetic macroangiopathy, we examined the progression of carotid artery intima-media thickness (IMT) as a surrogate end point.
Subjects with type 2 diabetes were divided into three groups, receiving the following treatments: (i) glibenclamide (n=59); (ii) gliclazide (n=30); and (iii) glibenclamide + metformin (n=29). Maximum IMT and average IMT (the greatest value among 6 average values of each 3 points including greatest thickness) were measured at the beginning and end of the observation period.
For the follow-up period of 3 years, the annual change in average IMT of the glibenclamide plus metformin group (0.003+/-0.048 mm) was smaller than that of the glibenclamide group (0.064+/-0.045 mm) and gliclazide group (0.032+/-0.036 mm) (p<0.0001 and p=0.043 respectively). In the gliclazide group, average IMT increased during the follow-up period, but annual change in average IMT was significantly smaller than that of the glibenclamide group (p=0.005). Glibenclamide + metformin or gliclazide also attenuated the progression of maximum IMT, compared with that of glibenclamide (0.041+/-0.105, 0.044+/-0.106, 0.114+/-0.131 mm/year respectively, p=0.029 and p=0.035 respectively). Multivariable regression analysis implied that administration of metformin or gliclazide significantly and independently (p<0.05) reduces the progression of average IMT, compared with glibenclamide monotherapy.
CONCLUSIONS/INTERPRETATION: These data indicate that metformin or gliclazide, rather than glibenclamide, have a potent anti-atherogenic effect in type 2 diabetes.
目的/假设：二甲双胍是一种广为人知的口服降糖药，常与磺脲类药物联合用于治疗2型糖尿病。然而，二甲双胍加磺脲类药物对糖尿病大血管病变的有益作用尚未明确。为评估磺脲类药物或磺脲类药物加二甲双胍是否能预防糖尿病大血管病变，我们将颈动脉内膜中层厚度（IMT）的进展作为替代终点进行了研究。
将2型糖尿病患者分为三组，分别接受以下治疗：（i）格列本脲（n = 59）；（ii）格列齐特（n = 30）；（iii）格列本脲 + 二甲双胍（n = 29）。在观察期开始和结束时测量最大IMT和平均IMT（每3个点的6个平均值中的最大值，包括最厚处）。
在3年的随访期内，格列本脲加二甲双胍组平均IMT的年变化（0.003±0.048 mm）小于格列本脲组（0.064±0.045 mm）和格列齐特组（0.032±0.036 mm）（分别为p < 0.0001和p = 0.043）。在格列齐特组中，随访期间平均IMT增加，但平均IMT的年变化明显小于格列本脲组（p = 0.005）。与格列本脲相比，格列本脲 + 二甲双胍或格列齐特也减缓了最大IMT的进展（分别为0.041±0.105、0.044±0.106、0.114±0.131 mm/年，p分别为0.029和0.035）。多变量回归分析表明，与单用格列本脲相比，使用二甲双胍或格列齐特可显著且独立地（p < 0.05）降低平均IMT的进展。
结论/解读：这些数据表明，在2型糖尿病中，二甲双胍或格列齐特而非格列本脲具有强大的抗动脉粥样硬化作用。
