Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes

AIMS: To simplify administration of aqueous exenatide once weekly, which requires reconstitution, the exenatide microspheres have been reformulated in a ready‐to‐use autoinjector with a Miglyol diluent (exenatide QWS‐AI). This study compared the efficacy and safety of exenatide QWS‐AI with the first‐in‐class glucagon‐like peptide‐1 receptor agonist exenatide twice daily (BID). MATERIALS AND METHODS: This randomized, open‐label, controlled study in patients with type 2 diabetes using diet and exercise or taking stable oral glucose‐lowering medication randomized patients 3:2 to either exenatide QWS‐AI (2 mg) or exenatide BID (10 μg) for 28 weeks. The primary outcome was the 28‐week change in glycated haemoglobin (HbA1c). A subset of patients completed a standardized meal test for postprandial and pharmacokinetic assessments. RESULTS: A total of 375 patients (mean HbA1c, 8.5% [69 mmol/mol]; body mass index, 33.2 kg/m(2); diabetes duration, 8.5 years) received either exenatide QWS‐AI (n = 229) or exenatide BID (n = 146); HbA1c was reduced by −1.4% and −1.0%, respectively (least‐squares mean difference, −0.37%; P = .0072). More patients achieved HbA1c <7.0% with exenatide QWS‐AI (49.3%) than with exenatide BID (43.2%; P = .225). Body weight was reduced in both groups (P = .37 for difference). Gastrointestinal adverse events (AEs) were reported in 22.7% (exenatide QWS‐AI) and 35.6% (exenatide BID) of patients; fewer patients in the exenatide QWS‐AI group withdrew because of AEs than in the exenatide BID group. Minor hypoglycaemia occurred most often with concomitant sulfonylurea use. CONCLUSIONS: Exenatide QWS‐AI was associated with a greater reduction in HbA1c, similar weight loss and a favorable gastrointestinal AE profile compared with exenatide BID.