Improved glycemic control and reduced bodyweight with exenatide: A double-blind, randomized, phase 3 study in Japanese patients with suboptimally controlled type 2 diabetes over 24 weeks

Aims/Introduction: To evaluate the efficacy and safety of the glucagon-like peptide-1 receptor agonist, exenatide, in Japanese patients with type 2 diabetes mellitus suboptimally controlled despite therapeutic doses of a sulfonylurea alone or combined with a biguanide or thiazolidinedione. Materials and Methods: Patients were randomized to a placebo or exenatide, either 5 or 10 mu g, given subcutaneously b.i.d. in addition to oral therapy. Patients randomized to 10 mu g exenatide received 5 mu g b.i.d. for the first 4 weeks, followed by 10 mu g b.i.d. for the last 20 weeks. Results: A total of 179 patients received the study drug and composed the full analysis set (n = 35, placebo; n = 72, exenatide 5 mu g; n = 72, exenatide 10 mu g; 68% male; 58 +/- 10 years; body mass index 25.5 +/- 4.1 kg/m2; HbA(1c) 8.2 +/- 0.9%; means +/- standard deviations). Baseline to end-point (least-squares means +/- standard errors) HbA(1c) changes (%) were -0.28 +/- 0.15 (placebo), -1.34 +/- 0.11 (exenatide 5 mu g) and -1.62 +/- 0.11 (exenatide 10 mu g) (both P < 0.001, exenatide vs placebo). Baseline to end-point bodyweight changes (kg) were -0.47 +/- 0.39 (placebo), -0.39 +/- 0.28 (exenatide 5 mu g) and -1.54 +/- 0.27 (exenatide 10 mu g; P = 0.026, exenatide 10 mu g vs placebo). Nausea, generally mild to moderate, was reported in 8.6% (placebo), 25.0% (exenatide 5 mu g) and 36.1% (exenatide 10 mu g) of patients. Mild to moderate hypoglycemia was reported in 22.9% (placebo), 51.4% (exenatide 5 mu g) and 58.3% (exenatide 10 mu g) of patients. Conclusions: Over 24 weeks, exenatide vs the placebo improved glycemic control, reduced bodyweight (10 mu g) and was well tolerated in Japanese patients with type 2 diabetes mellitus suboptimally controlled, despite oral therapy including a sulfonylurea. This trial was registered with ClinicalTrials.gov (no. NCT00577824). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00084.x, 2011).