Once-Weekly Exenatide Versus Once- or Twice-Daily Insulin Detemir: Randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas

摘要

OBJECTIVEdThis multicenter, open-label, parallel-arm study compared the efficacy andudsafety of exenatide once weekly (EQW) with titrated insulin detemir in patients with type 2uddiabetes inadequately controlled with metformin (with or without sulfonylureas).udRESEARCH DESIGN AND METHODSdPatients were randomized to EQW (2 mg) oruddetemir (once or twice daily, titrated to achieve fasting plasma glucose #5.5 mmol/L) for 26udweeks. The primary outcome was proportion of patients achieving A1C #7.0% and weight lossud$1.0 kg at end point, analyzed by means of logistic regression. Secondary outcomes includedudmeasures of glycemic control, cardiovascular risk factors, and safety and tolerability.udRESULTSdOf 216 patients (intent-to-treat population), 111 received EQW and 105 receiveduddetemir. Overall, 44.1% (95% CI, 34.7–53.9) of EQW-treated patients compared with 11.4%ud(6.0–19.1) of detemir-treated patients achieved the primary outcome (P , 0.0001). Treatmentudwith EQW resulted in significantly greater reductions than detemir in A1C (least-square mean 6udSE, 21.30 6 0.08% vs. 20.88 6 0.08%; P , 0.0001) and weight (22.7 6 0.3 kg vs. +0.8 6 0.4udkg; P , 0.0001). Gastrointestinal-related and injection site–related adverse events occurred moreudfrequently with EQW than with detemir. There was no major hypoglycemia in either group. Fiveud(6%) patients in the EQW group and six (7%) patients in the detemir group experienced minorudhypoglycemia; only one event occurred without concomitant sulfonylureas (detemir group).udCONCLUSIONSdTreatment with EQW resulted in a significantly greater proportion ofudpatients achieving target A1C and weight loss than treatment with detemir, with a low risk ofudhypoglycemia. These results suggest that EQW is a viable alternative to insulin detemir treatmentudin patients with type 2 diabetes with inadequate glycemic control using oral antidiabetes drugs.