Efficacy and Safety of Lixisenatide Once Daily Versus Exenatide Twice Daily in Type 2 Diabetes Inadequately Controlled on Metformin
A 24-Week, Randomized, Open-Label, Active-Controlled Study (GetGoal-X)
- Julio Rosenstock, MD1⇑,
- Denis Raccah, MD, PHD2,
- László Korányi, DSC3,
- Laura Maffei, MD4,
- Gabor Boka, MD5,
- Patrick Miossec, MD6 and
- John E. Gerich, MD7
- 1Dallas Diabetes and Endocrine Center at Medical City, Dallas, Texas
- 2University Hospital Sainte Marguerite, Marseille, France
- 3DRC Ltd, Balatonfüred, Hungary
- 4Investigación Clinica Aplicada, Buenos Aires, Argentina
- 5Sanofi R&D, Chilly-Mazarin, France
- 6Sanofi R&D, Paris, France
- 7University of Rochester School of Medicine, Rochester, New York
- Corresponding author: Julio Rosenstock, .
OBJECTIVE To compare efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled with metformin.
RESEARCH DESIGN AND METHODS Adults with diabetes inadequately controlled (HbA1c 7–10%) with metformin were randomized to lixisenatide 20 μg once daily (n = 318) or exenatide 10 μg twice daily (n = 316) in a 24-week (main period), open-label, parallel-group, multicenter study. The primary objective was a noninferiority assessment of lixisenatide versus exenatide in HbA1c change from baseline to week 24.
RESULTS Lixisenatide once daily demonstrated noninferiority in HbA1c reduction versus exenatide twice daily. The LS mean change was −0.79% (mean decrease 7.97 to 7.17%) for lixisenatide versus −0.96% (mean ± SD 7.96 to 7.01%) for exenatide, and treatment difference was 0.17% (95% CI, 0.033–0.297), meeting a predefined noninferiority upper CI margin of 0.4%. Responder rate (HbA1c <7.0%) and improvements in fasting plasma glucose were comparable. Both agents induced weight loss (from 94.5 to 91.7 kg and from 96.7 to 92.9 kg with lixisenatide and exenatide, respectively). Incidence of adverse events (AEs) was similar for lixisenatide and exenatide, as was incidence of serious AEs (2.8 and 2.2%, respectively). Discontinuations attributable to AEs occurred in 33 lixisenatide (10.4%) and 41 exenatide (13.0%) patients. In the lixisenatide group, fewer participants experienced symptomatic hypoglycemia (2.5 vs. 7.9%; P < 0.05), with fewer gastrointestinal events (especially nausea; 24.5 vs. 35.1%; P < 0.05).
CONCLUSIONS Add-on lixisenatide once daily in type 2 diabetes inadequately controlled with metformin demonstrated noninferior improvements in HbA1c, with slightly lower mean weight loss, lower incidence of hypoglycemia, and better gastrointestinal tolerability compared with exenatide twice daily.
- Received December 28, 2012.
- Accepted April 15, 2013.
- © 2013 by the American Diabetes Association.
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