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

Objective: This 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 methods: Patients 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.

Results: Of 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 ± SE, -1.30 ± 0.08% vs. -0.88 ± 0.08%; P < 0.0001) and weight (-2.7 ± 0.3 kg vs. +0.8 ± 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).

Conclusions: Treatment 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.

Figure 1

Study population, disposition, and demographics.

Figure 2

Change in glycemic control and body weight at end point and at specific time points over 26 weeks of treatment with EQW or insulin detemir (ITT population). A: LS mean ± SE change in A1C at 12, 18, and 26 weeks (MMRM used for analysis; data include patients with available data) and at end point (ANCOVA and last observation carried forward method used for analysis of change from baseline to end point). P indicated for treatment differences. *P < 0.0001. B: Proportion of patients who achieved target A1C of ≤7.4%, ≤7.0%, and ≤6.5%. C: LS mean ± SE change in body weight at weeks 4 to 26 and at end point (statistical methods same as those used for change in A1C); P indicated for treatment differences. *P = 0.0008 and **P < 0.0001. D: Scatter plot of A1C compared with change in weight at end point.