Factors moderating the effect of oral sulfonylureas on free water clearance

The effects of the antidiuretic agent chlorpropamide and the diuretic agent tolazamide on solute-free water clearance (CH2O) were compared in noninsulin-dependent diabetic patients undergoing water diuresis. Hyperglycemia (fasting serum glucose above 200 mg/dl) obscured the effects of these two sulfonylureas on CH2O. Thiazide or ethacrynic acid enhancement of chlorpropamide antidiuresis was also blunted by hyperglycemia and attendant osmotic diuresis. Thus, the low incidence of symptomatic hyponatremia during chlorpropamide treatment of diabetic patients may be explained by persistent hyperglycemia in such patients.