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

Abstract

OBJECTIVEdThis multicenter, open-label, parallel-arm study compared the efficacy and safety of exenatide once weekly (EQW) with titrated insulin detemir in patients with type 2 diabetes inadequately controlled with metformin (with or without sulfonylureas). RESEARCH DESIGN AND METHODSdPatients were randomized to EQW (2 mg) or detemir (once or twice daily, titrated to achieve fasting plasma glucose #5.5 mmol/L) for 26 weeks. The primary outcome was proportion of patients achieving A1C #7.0% and weight loss $1.0 kg at end point, analyzed by means of logistic regression. Secondary outcomes included measures of glycemic control, cardiovascular risk factors, and safety and tolerability. RESULTSdOf 216 patients (intent-to-treat population), 111 received EQW and 105 received detemir. Overall, 44.1% (95% CI, 34.7–53.9) of EQW-treated patients compared with 11.4% (6.0–19.1) of detemir-treated patients achieved the primary outcome (P , 0.0001). Treatment with EQW resulted in significantly greater reductions than detemir in A1C (least-square mean 6 SE, 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 0.4 kg; P , 0.0001). Gastrointestinal-related and injection site–related adverse events occurred more frequently with EQW than with detemir. There was no major hypoglycemia in either group. Five (6%) patients in the EQW group and six (7%) patients in the detemir group experienced minor hypoglycemia; only one event occurred without concomitant sulfonylureas (detemir group). CONCLUSIONSdTreatment with EQW resulted in a significantly greater proportion of patients achieving target A1C and weight loss than treatment with detemir, with a low risk of hypoglycemia. These results suggest that EQW is a viable alternative to insulin detemir treatment in patients with type 2 diabetes with inadequate glycemic control using oral antidiabetes drugs