Combination insulin and sulfonylurea therapy in insulin-requiring type 2 diabetes mellitus

To determine the effect(s) on glucose control, insulin dose, and circulating insulin levels of the addition of a sulfonylurea (glipizide) to the treatment regimen of patients with insulin-requiring type 2 diabetes mellitus.

Thirty seven patients with type 2 diabetes mellitus taking insulin for at least 1 year prior to study and treated with > or = 40 U of insulin per day were recruited for a randomized, double-blind, placebo-controlled, crossover trial. Patients were treated with 3 months of insulin + placebo (I + P) and 3 months of insulin + glipizide (I + G), with an intermediate 1 month washout period using insulin therapy alone. Adjustments were made initially to the maximum dose of glipizide (40 mg/day), followed by insulin dose adjustments. Twenty-nine of the 37 patients demonstrated a significant C-peptide response to Ensure and were selected for analysis.

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 hemoglobin was significantly different (9.8 I + G vs. 11.4% I + P, P < 0.008). The total daily insulin dose required was significantly lower with I + G (69.1 vs. 87.3 U, P < 0.0005). However, there were no significant differences in free insulin levels.

The addition of a sulfonylurea (glipizide) to insulin therapy in patients with insulin-requiring type 2 diabetes mellitus taking large doses of insulin results in a rapid and substantial improvement in glucose control despite a significant reduction in insulin dose. Therefore, this form of combination therapy should be considered for patients with the above characteristics whose diet and exercise programs are correct but whose response to insulin therapy is inadequate.