Oral sulfonylurea agents suppress hepatic glucose production in non-insulin-dependent diabetic individuals.

In the present paper we have reviewed the literature concerning the mechanisms of action of the oral sulfonylurea agents on glucose metabolism. In addition, we report our results examining the effect of glyburide in 10 non-insulin-dependent diabetic patients. Before therapy the fasting glucose concentration averaged 198 +/- 19 mg/dl and the oral glucose tolerance test (OGTT) was markedly abnormal. Following 3 mo of glyburide therapy, the fasting glucose had declined to 141 +/- 16 mg/dl (P less than 0.01 vs. preglyburide) and the OGTT (absolute plasma glucose concentration) was improved (P less than 0.001). However, the incremental increase (i.e., above basal) in plasma glucose during the OGTT was not significantly altered. In the postabsorptive state the fasting plasma glucose concentration is determined by only two factors: (1) the rate of glucose entry into the body, which is essentially equal to the rate of hepatic glucose production (HGP) and (2) the rate of glucose removal from the body or the glucose clearance. In the basal state HGP was slightly increased compared to age-matched controls and averaged 2.35 +/- 0.28 mg/kg X min. Following 3 mo of glyburide, HGP decreased to 1.72 +/- 0.18 mg/kg X min (P less than 0.01) and the decrease in HPG was strongly correlated with the decrease in fasting glucose (r = 0.85, P less than 0.005). Basal glucose clearance in non-insulin-dependent diabetes was reduced compared to controls (1.22 +/- 0.04 vs. 2.32 +/- 0.03 ml/kg X min, P less than 0.001) but did not change after glyburide (1.25 +/- 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)