COMPARATIVE EFFICACY OF A ONCE-DAILY CONTROLLED-RELEASE FORMULATION OF GLIPIZIDE AND IMMEDIATE-RELEASE GLIPIZIDE IN PATIENTS WITH NIDDM

OBJECTIVE - To compare the efficacy and safely of controlled-release g lipizide (glipizide-GITS [gastrointestinal therapeutic system]) and im mediate-release glipizide in patients with non-insulin-dependent diabe tes mellitus (NIDDM). RESEARCH DESIGN AND METHODS - In a multicenter, open-label, randomized, two-way crossover study, 132 patients with NID DM received daily doses of 5, 20, or 40 mg of either glipizide-GITS or immediate-release glipizide for 8 weeks followed by 8 weeks of the al ternate formulation. Plasma glucose, serum insulin, C-peptide, and pla sma glipizide levels were measured at fasting and post-Sustacal challe nge at the end of 1 and 8 weeks of each treatment phase. HbA(1c) was m easured at the end of weeks 7 and 8 of each treatment phase. RESULTS - Both formulations of glipizide yielded similar mean HbA(1c) values. H owever, mean fasting plasma glucose (FPG) levels were significantly lo wer with glipizide-GITS treatment than with immediate-release glipizid e at the end of week 1 (11.0 vs. 11.6 mmol/l; P < 0.01) and at the end of the 8-week treatment phase (10.9 vs. 11.7 mmol/l; P < 0.001). Fast ing insulin and C-peptide levels were lower after 5 mg glipizide-GITS vs. immediate-release glipizide. Glucose responses to Sustacal were si milar after both formulations of glipizide; however, serum insulin (P < 0.01) and C-peptide responses (P < 0.05) were lower with glipizide-G ITS than with immediate-release glipizide treatment at the end of the 8-week treatment phase. Mean plasma glipizide concentrations were stab le by the end of week 1, and the concentrations increased proportionat ely with dose. Once-daily Glipizide-GITS provided effective mean glipi zide concentrations (>50 ng/ml) 24 h after dosing, even at the lowest (5 mg) dose level. Both formulations were well tolerated. CONCLUSIONS - Glipizide-GITS was significantly more effective than immediate-relea se glipizide in reducing FPG levels. Both formulations reduced postpra ndial plasma glucose levels equally; however, glipizide-GITS exerted i ts control in the presence of lower plasma glipizide concentrations in addition to significantly lower insulin and C-peptide levels. This su ggests that glipizide-GITS improves insulin sensitivity.