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/m2; 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)

A 1-year safety study of dulaglutide in Japanese patients with type 2 diabetes on a single oral hypoglycemic agent: an open-label, nonrandomized, phase 3 trial

“…The most commonly reported treatment-emergent adverse events were nasopharyngitis and gastrointestinal disorders, such as constipation, diarrhea, nausea, and vomiting. The adverse event profile was generally consistent with other studies evaluating GLP-1 receptor agonists in Asian patients [25][26][27][28][29][30]. The incidence of diarrhea in the DU 0.75+BG group (14.8%) was higher than in the other combination therapy groups (range 4.6 to 9.9%).…”

The Use of Exenatide in Managing Markers of Cardiovascular Risk in Patients with Type 2 Diabetes: A Systematic Review

“…All the eleven studies [19,20,21,22,23,24,25,26,27,28,29] (Table 1) for this review were multicentre and randomised controlled studies involving patients with type 2 diabetes. While seven of the studies [19,21,22,23,25,27,28] were conducted in at least 2 countries, the remaining 4 [20,24,26,29] were conducted in Italy, Japan, the US and Germany respectively.…”

“…While seven of the studies [19,21,22,23,25,27,28] were conducted in at least 2 countries, the remaining 4 [20,24,26,29] were conducted in Italy, Japan, the US and Germany respectively. However, all eleven studies had background treatment in addition to the intervention treatments except the study by Gastaldelli et al [19].…”

“…Exenatide twice daily was compared to placebo in seven of the 11 studies [19,20,21,22,23,24,25] (Table 1). …”

Effect of GLP-1 receptor agonists on waist circumference among type 2 diabetes patients: a systematic review and network meta-analysis

“…Another trial in 69 T2DM patients demonstrated the significant reduction of waist circumference in exenatide treatment for 1 year [43]. Several trials indicated significant decrease in waist/hip ratio associated with GLP-1RAs [28,32,37]. Modest reduction in waist circumference has been proved to be clinically meaningful for T2DM patients [13,14].…”