Free radical scavenging activity of sulfonylureas: a clinical assessment of the effect of gliclazide.
In long-term clinical studies the beneficial effects of gliclazide on platelets have been related to a reduction in oxidative stress. This property is because of gliclazide's free radical scavenging ability that relates to the unique amino azabicyclo-octare ring, which is grafted on to the sulfonylurea. During a blinded clinical trial, the possible effects of gliclazide were assessed in 30 non-insulin-dependent diabetic patients. All patients had been treated for diabetes for more than 2 years (mean 8 years) and had been established on glibenclamide for over 2 years with or without adjunctive metformin therapy. Patients were studied for 6 months and randomized to continue either their present dose of glibenclamide or to be converted to an equipotent dose of gliclazide. Measurements were taken of hemostatic variables, the oxidative status of the plasma, and the redox status, both extracellularly as plasma albumin-thiols (PSH) and lipid peroxides, and intracellularly as red blood cell superoxide dismutase activity (SOD). At 3 months, diabetic control was unaltered, but there were significant improvements in the oxidative status of the gliclazide-treated patients. Lipid peroxides decreased (8.3 +/- 1.1 to 7.0 +/- .06 micromol/L, P < .01) and red blood cell SOD increased (135 +/- 21 to 152 +/- 36 microg/mL, P < .05). PSH levels were unaltered at 458 +/- 38 micromol/L, whereas they had decreased significantly in the glibenclamide patients (414 +/- 34 micromol/L, P < .05), resulting in a significant difference between the 2 treatment groups (P < .004). Platelet reactivity to collagen also improved in the gliclazide-treated patients, decreasing from 65.1% +/- 14% to 50.8% +/- 24% (P < .01). The reactivity of the platelets remained unaltered in the glibenclamide patients. At 6 months, the significant differences between the 2 treatment groups remained. Hence, gliclazide was shown in a clinical study to have free radical scavenging activity independent of glycemic control.
Jennings
P E
PE
Department of Medicine, York District Hospital, UK.
Belch
J J
JJ
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005907:Gliclazide / Q000627:therapeutic use*; D005905:Glyburide / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
D016166:Free Radical Scavengers; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D003094:Collagen; D008687:Metformin; D005907:Gliclazide; D005905:Glyburide