Effect of glipizide GITS on insulin sensitivity, glycemic indices, and abdominal fat composition in NIDDM

Glipizide in a once daily formulation utilizing the gastrointestinal therapeutic system (GITS) has been shown in preliminary studies to improve insulin sensitivity as assessed with meal tolerance testing. To evaluate the ability of glipizide GITS to specifically improve clinical insulin sensitivity in vivo, a double-blind, placebo-controlled trial randomized 40 NIDDM subjects to either glipizide GITS or placebo. The study was designed to evaluate NIDDM subjects whose fasting blood glucose was <190 mg% and GHb < 11% to avoid the adverse effects of hyperglycemia on insulin resistance and secretion. After screening, oral hypoglycemic agents were discontinued for one month, at which time a meal tolerance test with glucose and insulin response, glycated hemoglobin, and fructosamine were obtained. Insulin sensitivity (S-I) and glucose effectiveness (S-g) were determined with a 4-h frequently sampled intravenous tolerance test (modified minimal model - 3rd phase insulin infusion) at baseline. Specific abdominal fat depots were quantitated by MRI scans. Patients were then randomized to receive placebo or active drug and all parameters were repeated at 1, 2, 5, and 8 months after randomization. Glipizide GITS significantly improved meal tolerance, reduced glycated blood proteins, and increased insulin sensitivity (P <.001). No change was seen for S-G. There was no significant change in abdominal fat distribution during the trial. Glipizide CITS is effective in lowering glucose tolerance and improving insulin sensitivity without an increase in fasting insulin, weight gain, or change in abdominal fat composition. (C)1998 Wiley-Liss, Inc.