Efficacy and safety of autoinjected exenatide once‐weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: The DURATION‐NEO‐2 randomized clinical study

AIMS: Glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors treat type 2 diabetes through incretin‐signaling pathways. This study compared the efficacy and safety of the glucagon‐like peptide‐1 receptor agonist exenatide once‐weekly (Miglyol) suspension for autoinjection (QWS‐AI) with the dipeptidyl peptidase‐4 inhibitor sitagliptin or placebo. MATERIALS AND METHODS: In this open‐label, multicentre study of patients with type 2 diabetes who had suboptimal glycaemic control on metformin monotherapy, 365 patients were randomized to receive exenatide 2.0 mg QWS‐AI, sitagliptin 100 mg once daily or oral placebo (3:2:1 ratio). The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to 28 weeks. RESULTS: At 28 weeks, exenatide QWS‐AI significantly reduced HbA1c from baseline compared to sitagliptin (−1.13% vs −0.75% [baseline values, 8.42% and 8.50%, respectively]; P = .02) and placebo (−0.40% [baseline value, 8.50%]; P = .001). More exenatide QWS‐AI‐treated patients achieved HbA1c <7.0% than did sitagliptin‐ or placebo‐treated patients (43.1% vs 32.0% and 24.6%; both P < .05). Exenatide QWS‐AI and sitagliptin reduced fasting plasma glucose from baseline to 28 weeks (−21.3 and −11.3 mg/dL) vs placebo (+9.6 mg/dL), with no significant difference between the 2 active treatments. Body weight decreased with both active treatments (−1.12 and −1.19 kg), but not with placebo (+0.15 kg). No improvement in blood pressure was observed in any group. The most common adverse events with exenatide QWS‐AI were gastrointestinal events and injection‐site reactions. CONCLUSIONS: This study demonstrated that exenatide QWS‐AI reduced HbA1c more than sitagliptin or placebo and was well tolerated.