It is certainly acknowledged, albeit rather recently, that adequate control of hyperglycemia in type II diabetic patients is generally poor at best. A heightened realization of this fact and hopes that control of hyperglycemia may prevent complications or limit their severity have spawned newer approaches toward achieving improved glycemic control through changes in standard programmatic care with diet, exercise, oral agents or insulin therapy, and management of hypertension and obesity. Insulin taken at bedtime to control nocturnal hepatic glucose output, multiple doses of regular insulin coupled with frequent blood sugar measurements, and combined insulin and oral agents are approaches currently under trial in several centers. Interest in combination therapy stems in part from residual concern that hyperinsulinemia may contribute to the development of atherosclerosis, and to evidence that the sulfonylureas, especially the second-generation drugs, improve sensitivity to the glycolytic effects of insulin, thereby reducing insulin resistance. More than a dozen serious studies of combined therapy have been reported since the early 1980s. This study is unique, however, in several respects since non-obese, type II, insulin-requiring diabetic persons were chosen for study and were hospitalized prior to initiating the actual investigation in order to secure optimal diabetic control and thereby ensure greater sensitivity of the beta cell. Twenty type II diabetic patients were studied in a double-blinded, placebo-controlled trial with insulin and glyburide. All were treated with intermediate-acting insulin and adjustments were made as necessary to achieve optimal control, after which the patients were randomly assigned to either an insulin-and-glyburide program or to insulin-plus-placebo treatment. Thereafter, patients were followed in an outpatient setting for four months, after which time they were rehospitalized for final assessment. Standard chemistries, urinary glucose, glycosylated hemoglobins, and urinary C-peptide levels were measured. The fasting serum glucose level remained normal in the glyburide/insulin-treated group, whereas these were significantly higher in the placebo-plus-insulin group at four and at eight weeks. Glycosylated hemoglobin levels rose progressively in the placebo- and insulin-treated group and by 16 weeks were significantly higher than measurements from the insulin- and glyburide-treated group of patients (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)