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

Abstract

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 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.

Long-Term Effects of Pioglitazone on Carotid Atherosclerosis in Japanese Patients with Type 2 Diabetes without a Recent History of Macrovascular Morbidity

“…The number of patients treated was based on the assumption of a change of 0.022 mm in the non-pioglitazone group, whereas the actual differences were 0.031 and 0.043 mm. This significant decrease even in the non-pioglitazone group possibly reflects the more frequent use of biguanides and -glucosidase inhibitors in the non-pioglitazone group 24,25) . Interestingly, the findings of this substudy mirror the results of the "parent" PROBE trial, which also found a non-significant trend towards improved macrovascular outcomes in the pioglitazone group versus the control group 15) .…”

Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin

“…A possible explanation for this discrepancy may be the fact that not all patients who lose weight experience reductions in their plasma renin and aldosterone levels (28,29). However, metformin is known to positively affect other parameters which influence the development of cardiovascular disease, regardless of any effect on BP (30,31). Our results agree with the literature regarding the effect of metformin on BMI reduction (9,12,13), reduction of daily insulin dose (9,12,13), biguanide-related sideeffects (21,24), and reduction of WC, which is a cornerstone for the diagnosis of metabolic syndrome and may play the role of a co-variate when other parameters are analyzed (18,32).…”

The use of gliclazide in the mirror of the individualized sulfonylurea therapy

“…A PDX-1-expressziót gén-és fehérjeszinten egyaránt serkentette [29]. Endotheldiszfunkciót mérséklő, egyes gyulladásos tényezők képződését gátló, valamint a kísérletes körülmények kö-zött észlelt, érfali lipidlerakódást mérséklő hatásával magyarázzák az atherogenesist más SU-származékokéhoz képest lassító természetét [7]. Experimentális vizsgálat-ban igazolták nitrogén-monoxid-dependens vasodilatatiót serkentő [32,33], sőt streptozotocinnal kiváltott diabetesben, vérnyomást csökkentő tulajdonságát is [33].…”

“…Az adatok értékelését nehezíti azonban, hogy az ismeretek nagy része experimentális megfi gyelésekből származik, továbbá, hogy pros pektív tanulmányokból származó "kemény végpontú" eredmé-nyek, illetve az egyes származékokat összehasonlító ("head-to-head") vizsgálatok nem, illetve csak korláto-zottan állnak rendelkezésre. Kétségtelen ugyanakkor, hogy egyre bővül a SU-hatás biokémiai hátterével kapcsolatos ismeretek köre [4,5,6], s nő a pancreasszelektívnek tartott származékok (a második generációs vegyü-letek közül a gliclazid) klinikai előnyeiről beszámoló közlemények [7,8,9,10] száma is.…”