GLICLAZIDE POTENTIATES SUPPRESSION OF HEPATIC GLUCOSE-PRODUCTION IN NON-INSULIN-DEPENDENT DIABETIC-PATIENTS

The mechanism of the hypoglycemic action of gliclazide was evaluated i n 17 diet-treated non-insulin-dependent diabetes mellitus (NIDDM) pati ents. In study A, five patients received a 240-minute glucose infusion along with [3-H-3]glucose infusion. In study B, seven patients receiv ed a 240-minute isoglycemic insulin clamp along with [3-H-3]glucose in fusion. And in study C, five patients received a somatostatin infusion with basal replacing doses of insulin and glucagon. The three studies (A, B, and C) were repeated twice. Gliclazide (240 mg orally) was adm inistered on one occasion, and placebo was given on the second occasio n. Basal hepatic glucose production (HGP) and utilization and plasma g lucose, insulin, C-peptide, glucagon, and free fatty acid (FFA) concen trations were similar before administration of gliclazide and placebo. In study A, plasma glucose, its incremental area, and HGP were reduce d by gliclazide administration (all P < .05), but glucose utilization was not significantly affected. The increase in plasma insulin and C-p eptide concentrations was similar with gliclazide and placebo, althoug h the plasma insulin to glucose ratio was increased with gliclazide. H GP decremental area was correlated with the reduction in plasma glucos e incremental area (r = -.63, P < .05). In study B, gliclazide adminis tration produced a larger suppression of HGP, but the overall rate of glucose utilization was not different in the two studies. In study C, plasma glucose concentration and HGP progressively decreased in both s tudies, without a difference between gliclazide and placebo. These res ults suggest that under conditions of hyperglycemia and hyperinsulinem ia gliclazide elicits a larger suppression of HGP. Copyright (C) 1996 by W.B. Saunders Company