Metformin or gliclazide, rather than glibenclamide, attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes

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. Methods. 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. Results. For the follow-up period of 3 years, the annual change in average IMT of the glibenclamide plus metformin group (0.003 +/- 0.048 min) was smaller than that of the glibenclamide group (0.064 +/- 0.045 min) 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.