Effect of exenatide on 24-hour blood glucose profile compared with placebo in patients with type 2 diabetes: a randomized, double-blind, two-arm, parallel-group, placebo-controlled, 2-week study.

Abstract Objective: The aim of this study was to examine the glucose-lowering effect of exenatide over 24 hours in patients with type 2 diabetes with inadequate glycemic control using metformin, with or without a thiazolidinedione (TZD). Methods: This randomized, double-blind, 2-arm, parallel-group, placebo-controlled, 2-week study was conducted in patients with type 2 diabetes with inadequate glycemic control, despite metformin with or without a TZD. Patients underwent a baseline and a week-2 (study end) 24-hour admission during which serial serum glucose measurements were taken. Preprandial and postprandial concentrations of triglycerides and free fatty acids were also measured. Meals provided for each patient were identical at the baseline and week-2 assessments. Following the baseline admission, patients were randomized to receive SC injections of either exenatide (5 μg BID for 1 week, then 10 μg BID for the next week) or placebo (volume equivalent) for 14 days. Results: A total of 30 patients (19 women [63%], 11 men [37%]; mean [SD] age, 52.6 [11.2] years; weight, 94.3 [23.0] kg; body mass index, 34.2 [6.1] kg/m 2 ; glycosylated hemoglobin value, 8.0% [0.9%]; diabetes duration, 8.7 [5.6] years; race, Hispanic 18 [60%], white 10 [33%], black 2 [7%]) were eligible. Seventeen patients (57%) were randomized to treatment with exenatide and 13 patients (43%) received placebo. Concurrent antidiabetic medications were metformin only (n = 19 [63%]) and metformin plus a TZD (n = 11 [37%]). All postbaseline values were least squares mean (SE). After 2 weeks (study end), the 24-hour time-average glucose values were 7.0 (0.2) and 8.8 (0.3) mmol/L for exenatide-treated and placeboadministered patients, respectively ( P P P = 0.001), and the evening meal (6.8 [0.4] vs 11.3 [0.4] mmol/L; P 7.8 and >11.1 mmol/L were significantly shorter for the exenatide group compared with the placebo group (>7.8 mmol/L: 6.8 [0.9] vs 14.1 [1.1] hours; >11.1 mmol/L: 1.0 [0.7] vs 4.7 [0.8] hours; both, P Conclusions: In these patients with type 2 diabetes, exenatide was associated with significantly reduced glucose concentrations at multiple time points during 24 hours, with the greatest effect seen on postprandial glucose concentrations. In addition, exenatide was associated with decreased overall hyperglycemic exposure and significantly decreased postprandial triglyceride excursions. These results are consistent with those seen in other studies that reported the effectiveness of exenatide in controlling hyperglycemia in patients with type 2 diabetes.