Vildagliptina e gliclazida na resposta glicêmica, nos marcadores de inflamação e de estresse oxidativo em DM2 inadequadamente controlados com metformina

Abstract

Diabetes mellitus has a latent baseline inf lammatory status and high oxidative stress that are intrinsically related to complications of the disease. Recent studies have shown anti - inflammatory actions and reducing oxidative stress, independent of glycemic beneficial effect, using incretin based th erapy. The present study aimed to evaluate and compare the response of gliclazide, second - generation sulfonylurea, and vildagliptin, DPP - 4 inhibitor, in the inflammatory markers and in the oxidative stress in type 2 diabetic patients inadequately controlle d with metformin. T his is a clinical prospective, randomized, open - label , comparative study with 35 patients with 22 weeks duration Eighteen patients were given gliclazide MR , 60 - 120mg/day , and 17 patients used the vildagliptin, 100 mg/day. Fasting and pos tprandial, HbA1c, insulin, glucagon, GLP - 1, HOMA - IR, soluble markers of cell adhesion (VCAM, ICAM and E - selectin), inflammatory markers (TNF - alpha, IL - 6 and PAI - 1) and of oxidative stress (TBARS and TAOS) were measured at the beginning and at the end of th e study. The study was undertaken by 51.4% of males and the average age (years) of participants was 56.9 ± 10.0. No statistical difference was observed at study in weight and BMI, but there was a positive change in mean weight and BMI found in the gliclazi de group (+ 1.4kg and + 0.6kg/m 2 , respectively) and negative change in the vildagliptin group ( - 0,6Kg and - 0,3Kg/m 2 , respectively). There was better control of fasting and postprandial glycemia in the gliclazide group ( ajusted p <0.001 and = 0.008, respecti vely) and both drugs showed similar improvement in glycated (p = 0.068) . The sE - selectin was the only marker that showed a significant decrease and was only intragroup (p = 0.009, vildagliptin group). Insulin significantly reduced in favor of the vildaglip tin group ( 23,4 ± 11,1 vs 17,8 ± 11,9 μ U/ml , ajusted p = 0.020) and also glucagon (77.7 ± 44.0 vs 46, 4 ± 31.7, ajusted p = 0.012). There was a significant increase of GLP - 1 in the vildagliptin intragroup (p = 0.028) and a significant decline in HOMA also in the vildagliptin intragroup (p = 0.003). The PAI - 1 did not show significant changes in the study; TNF - alpha was significantly reduced in both intragroup treatments (3.9 ± 0.7 to 3.5 ± 1,1pg/ml, p = 0.006, gliclazide group and 3.6 ± 1.2 to 3.0 ± 1,5pg/ml, p <0.001, vildagliptin) group, with intergroup significance favoring vildagliptin ( ajusted p = 0.001). The IL - 6 had no significant increase in the gliclazide group and also not significant reduction in the vildagliptin group. The TBARS showed improvement in both groups, with significance in the vildagliptin intragroup (9.1 ± 1.6 to 8.0 ± 0.7 nmol/MDA /ml), p = 0.039), and intergroup significance favoring vildagliptin (8.4 ± 0 9 vs 8.0 ± 0.7 nmol/MDA/ml, ajusted p <0.001, gliclazide and vildagliptin, respective ly) and the TAOS also showed improvement in both groups, but not statistically significant. Gliclazide showed better response in fasting and postprandial glycemia and both drugs improved similarly glycated. Vildagl iptin improves glycemic control with less need for insulin and lower HOMA - IR and was more effective in reducing inflammation and improving oxidative stress.