COMBINATION INSULIN AND SULFONYLUREA THERAPY IN INSULIN-REQUIRING TYPE-2 DIABETES-MELLITUS

Purpose: To determine the effect(s) on glucose control, insulin dose, and circulating insulin levels of the addition of a sulfonylurea (glip izide) to the treatment regimen of patients with insulin-requiring typ e 2 diabetes mellitus. Patients and Methods: Thirty seven patients wit h type 2 diabetes mellitus taking insulin for at least 1 year prior to study and treated with greater than or equal to 40 U of insulin per d ay were recruited for a randomized, double-blind, placebo-controlled, crossover trial. Patients were treated with 3 months of insulin + plac ebo (I + P) and 3 months of insulin + glipizide (I + G) with an interm ediate 1 month washout period using insulin therapy alone. Adjustments were made initially to the maximum dose of glipizide (40 mg/day), fol lowed by insulin dose adjustments. Twenty-nine of the 37 patients demo nstrated a significant C-peptide response to Ensure(R) and were select ed for analysis. Results: The Fasting plasma glucose in the I + G arm was 6.8 (121.8 mg/dl) vs. 8.7 mmol/L (156.0 mg/dl) in the I + P arm, P < 0.001. Mean plasma glucose over 24 hours was 9.8 (176.9 mg/dl) for I + G vs. 11.3 mmol/L (203.8 mg/dl) for I + P, P < 0.001. Glycated hem oglobin was significantly different (9.8 I + G vs. 11.4% I + P, P < 0. 008). The total daily insulin dose required was significantly lower wi th I + G (69.1 vs. 87.3 U, P < 0.0005). However, there were no signifi cant differences in free insulin levels. Conclusion: The addition of a sulfonylurea (glipizide) to insulin therapy in patients with insulin- requiring type 2 diabetes mellitus taking large doses of insulin resul ts in a rapid and substantial improvement in glucose control despite a significant reduction in insulin dose. Therefore, this form of combin ation therapy should be considered for patients with the above charact eristics whose diet and exercise programs are correct but whose respon se to insulin therapy is inadequate. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.