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

Abstract

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 μg, given subcutaneously b.i.d. in addition to oral therapy. Patients randomized to 10 μg exenatide received 5 μg b.i.d. for the first 4 weeks, followed by 10 μg 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 μg; n = 72, exenatide 10 μg; 68% male; 58 ± 10 years; body mass index 25.5 ± 4.1 kg/m(2); HbA1c 8.2 ± 0.9%; means ± standard deviations). Baseline to end-point (least-squares means ± standard errors) HbA1c changes (%) were -0.28 ± 0.15 (placebo), -1.34 ± 0.11 (exenatide 5 μg) and -1.62 ± 0.11 (exenatide 10 μg) (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 μg) and -1.54 ± 0.27 (exenatide 10 μg; P = 0.026, exenatide 10 μg vs placebo). Nausea, generally mild to moderate, was reported in 8.6% (placebo), 25.0% (exenatide 5 μg) and 36.1% (exenatide 10 μg) of patients. Mild to moderate hypoglycemia was reported in 22.9% (placebo), 51.4% (exenatide 5 μg) and 58.3% (exenatide 10 μg) of patients.

Conclusions: Over 24 weeks, exenatide vs the placebo improved glycemic control, reduced bodyweight (10 μg) 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).

Keywords: Exenatide; Glycemic control; Japanese.

Figures

Figure 1

Patients’ dispositions.

Figure 2

Mean changes of HbA1c from baseline to each visit. Data are mean ± SD for the full analysis set. The dotted line represents the baseline value.

Figure 3

Percentage of patients who received placebo, exenatide 5 μg or exenatide 10 μg achieving HbA1c <7.0% or <6.5% at end‐point.

Figure 4

Mean changes of fasting blood glucose from baseline to each visit. Data are means ± SD for full analysis set. The dotted line represents the baseline value.

Figure 5

Effects of (a) placebo, (b) exenatide 5 μg and (c) exenatide 10 μg on 7‐point self‐monitored blood glucose at end‐point. Data are means ± SD for the full analysis set.

Figure 6

Change in bodyweight from baseline to end‐point. Data are least square (LS) means − SE for the full analysis set. *P = 0.026 vs placebo.