A double-blind randomized comparison of meal-related glycemic control by repaglinide and glyburide in well-controlled type 2 diabetic patients.
OBJECTIVE: This study was designed to compare diurnal blood glucose excursions and the effects of accidental dietary noncompliance in type 2 diabetic patients who are well-controlled on either repaglinide or glyburide treatment. RESEARCH DESIGN AND METHODS: This single-center double-blind randomized study comprised type 2 diabetic patients whose mean fasting blood glucose value after repaglinide/glyburide titration and stabilization was in the range of 90-140 mg/dl. The study consisted of an initial screening day, a titration period of 3 weeks, a 1-week stabilization period, a study period, and an end-of-study day. During the 3-day study period, half the patients of each group received two meals on the first day and three meals on the next 2 days, and in the other half, this sequence was reversed. Repaglinide was administered preprandially with each meal, and glyburide was administered as recommended in current labeling, i.e., either one or two daily doses before breakfast and dinner, regardless of whether lunch had been omitted. The diurnal blood glucose excursions on a day in which three meals were eaten were compared between the two groups, and the minimum blood glucose concentration (BGmin) measurements were compared between lunch and dinner on days with three and two meals. RESULTS: Of the 83 randomized patients, 43 entered into the 3-day study period and completed the trial. The results showed no significant differences between the repaglinide and glyburide groups in average blood glucose excursions from fasting blood glucose (P = 0.44). The influence on the mean BGmin of omitting a meal differed significantly between the repaglinide and glyburide groups (P = 0.014). In the latter group, BGmin decreased from 77 to 61 mg/dl as a result of omitting lunch, whereas in the repaglinide group, BGmin was unchanged for the two-meal day (78 mg/dl) and the three-meal day (76 mg/dl). All hypoglycemic events (n = 6) occurred in the glyburide group on the two-meal day, in connection with omitting lunch. No hypoglycemic events were recorded in the repaglinide group. CONCLUSIONS: These results suggest that treatment with repaglinide in well-controlled type 2 diabetic patients who miss or delay a meal is superior to treatment with longer-acting sulfonylurea drugs (such as glyburide) with respect to the risk of hypoglycemic episodes.