IN MOST POORLY CONTROLLED GLYBURIDE-TREATED TYPE-2 DIABETIC-PATIENTS DRUG-WITHDRAWAL CAUSES FURTHER INCREASE IN GLYCEMIA NOT ACCOMPANIED BYCHANGES IN INSULIN-SECRETION

To find out whether the secondary failure of glyburide in type 2 diabe tes is complete or partial, we studied 38 patients, age (M +/- SD) 69 +/- 9 years, suffering from diabetes for 13.5 +/- 8.4 years and treate d with glyburide for 5-13 years, with poor glycemic control (glycohemo globin 10.6 +/- 2.6%). Serum glucose, insulin and C-peptide were assay ed before and 1 h and 2 h after a simulated meal load (355 Cal), after which the drug was replaced with placebo for 4 weeks, and the test re peated. After glyburide withdrawal, fasting glycemia increased from 10 .3 +/- 3.3 to 15.1 +/- 4.4 mmol/L < 0.001), but in 3/38 patients, it e ven decreased and in five others the changes were less than +/- 2 mmol /L. These changes negatively but only weakly correlated with initial g lycemia: r = 0.4123, p < 0.010. The mean post-meal glycemia at 1 h and 2 h increased respectively by 3.3 and 5.9 mmol/L (both p < 0.001). Ne ither the levels of glycemia nor its changes after the glyburide withd rawal correlated with the levels of, or changes in, insulin or C-pepti de. We conclude that in most but not all type-2 diabetic patients, poo rly controlled with glyburide, the drug still retains some limited the rapeutic effectiveness, and therefore its withdrawal causes further de terioration of control with the almost equal increases in fasting and post-meal levels of glycemia. These changes are not accompanied by dec rease in insulin secretion.