Concomitant insulin and sulfonylurea therapy in patients with type II diabetes. Effects on glucoregulation and lipid metabolism

Abstract

Recent evidence suggests concomitant insulin and sulfonylurea therapy has a theoretical potential in the management of type II diabetes mellitus. In a long-term double-blind, randomized placebo-controlled study of combination therapy, serum glucose, C-peptide, total cholesterol, triglyceride, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations were evaluated in insulin-treated patients with poorly controlled, type II diabetes mellitus after addition of either glyburide (n = 10) or placebo (n = 12). Oral glucose tolerance testing was performed at weeks 0, 4, and 16. Clinical characteristics and glycemic control (fasting blood glucose and glycosylated hemoglobin values) were similar at week 0 in both groups. The placebo group had no change in any metabolic parameter throughout the study period. At week 4, glyburide significantly lowered fasting blood glucose and integrated glucose areas (p less than 0.01) compared with values at week 0 (fasting blood glucose 225 +/- 20 versus 286 +/- 27 mg/dl, p less than 0.02). Mean fasting, stimulated, and integrated C-peptide levels were significantly higher (p less than 0.02) at week 4 versus week 0. At week 16, mean fasting blood glucose values remained significantly lower compared with baseline values (252 +/- 25 versus 286 +/- 27 mg/dl, p less than 0.05). Glycosylated hemoglobin levels decreased significantly (p less than 0.05) at weeks 4 to 16 compared with the baseline values. Although glucose responses and integrated areas were no different after oral glucose tolerance testing, fasting and stimulated C-peptide levels were significantly higher (p less than 0.05) at week 16 versus week 0. Lipid and lipoprotein levels remained unchanged. In summary, combination therapy consisting of glyburide and insulin moderately improved glucose control in type II diabetes mellitus at the end of four weeks. Despite significantly lower fasting serum glucose and glycosylated hemoglobin levels after 16 weeks, combination treatment did not normalize glycemic control. Glucose tolerance decreased further after 16 weeks despite persistence of increased endogenous insulin secretion. The role of the combination therapy in the long-term care of patients with type II diabetes mellitus needs further investigation.