g of fasting blood glucose and by HbA1c at the end of the study. HbA1c for the PRANDIN- treated groups (1 and 4 mg groups combined) at the end of the study was decreased compared to the placebo-treated group in previously napatients and in patients previously treated with oral hypoglycemic agents by 2.1% units and 1.7% units, respectively. In this fixed-dose trial, patients who were nato oral hypoglycemic agent therapy and patients in relatively good glycemic control at baseline (HbA1c below 8%) showed greater blood glucose-lowering including a higher frequency of hypoglycemia. Patients who were previously treated and who had baseline HbA1c8% reported hypoglycemia at the same rate as patients randomized to placebo. There was no average gain in body weight when patients previously treated with oral hypoglycemic agents were switched to PRANDIN. The average weight gain in patients treated with PRANDIN and not previously treated with sulfonylurea drugs was 3.3%.
PRANDIN was compared to other insulin secretagogues in 1-year controlled trials to demonstrate comparability of efficacy and safety. Hypoglycemia was reported in 16% of 1228 PRANDIN patients, 20% of 417 glyburide patients, and 19% of 81 glipizide patients. Of PRANDIN-treated patients with symptomatic hypoglycemia, none developed coma or required hospitalization.
Combination Trials
PRANDIN was studied in combination with metformin in 83 patients not satisfactorily controlled on exercise, diet, and metformin alone. PRANDIN dosage was titrated for 4 to 8 weeks, followed by a 3-month maintenance period. Combination therapy with PRANDIN and metformin resulted in significantly greater improvement in glycemic control as compared to repaglinide or metformin monotherapy. HbA1c was improved by 1% unit and FPG decreased by an additional 35 mg/dL. In this study where metformin dosage was kept constant, the combination therapy of PRANDIN and metformin showed dose-sparing effects with respect to PRANDIN. The greater efficacy response of the combination group was achieved at a lower daily repaglinide dosage than in the PRANDIN monotherapy group (see Table).
PRANDIN and Metformin Therapy: Mean Changes from Baseline in Glycemic Parameters and Weight after 4 to 5 Months of Treatment*
*based on intent-to-treat analysisp < 0.05, for pairwise comparisons with PRANDIN and metformin.p < 0.05, for pairwise comparison with metformin.PRANDINCombinationMetforminN282727Median Final Dose (mg/day)126 (PRANDIN) 1500 (metformin)1500HbA1c (% units)-0.38-1.41-0.33FPG (mg/dL)8.8-39.2-4.5Weight (kg)3.02.4-0.90A combination therapy regimen of PRANDIN and pioglitazone was compared to monotherapy with either agent alone in a 24-week trial that enrolled 246 patients previously treated with sulfonylurea or metformin monotherapy (HbA1c > 7.0%). Numbers of patients treated were: PRANDIN (N = 61), pioglitazone (N = 62), combination (N = 123). PRANDIN dosage was titrated during the first 12 weeks, followed by a 12-week maintenance period. Combination therapy resulted in significantly greater improvement in glycemic control as compared to monotherapy (figure below). The changes from baseline for completers in FPG (mg/dL) and HbA1c (%), respectively were: -39.8 and -0.1 for PRANDIN, -35.3 and -0.1 for pioglitazone and -92.4 and -1.9 for the combination. In this study where pioglitazone dosage was kept constant, the combination therapy group showed dose-sparing effects with respect to PRANDIN (see figure lege |
