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

Melanie Davies; Simon Heller; Seamus Sreenan; Hélène Sapin; Omolara Adetunji; Arash Tahbaz; Jiten Vora

doi:10.2337/dc12-1333

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

Melanie Davies, MBCHB, MD, FRCP¹ ⇓,
Simon Heller, DM, FRCP²,
Seamus Sreenan, MBBCH, FRCPI, MD³,
Hélène Sapin, MSC⁴,
Omolara Adetunji, MBBS, FWACP⁵,
Arash Tahbaz, MBCHB, MRCP⁵ and
Jiten Vora, MA, MD, FRCP⁶

¹Department of Cardiovascular Sciences, University of Leicester, Leicester, U.K.
²Academic Unit of Diabetes, Endocrinology and Metabolism, The University of Sheffield, Sheffield, U.K.
³Department of Endocrinology, Royal College of Surgeons in Ireland, Connolly Hospital, Dublin, Ireland
⁴Lilly France, Suresnes Cédex, France
⁵Eli Lilly and Company, Basingstoke, U.K.
⁶Diabetes Centre, Royal Liverpool University Hospitals, Liverpool, U.K.

Corresponding author: Melanie Davies, melanie.davies{at}uhl-tr.nhs.uk.

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.

Received July 6, 2012.
Accepted November 5, 2012.

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