ArticlesExenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomised controlled trial
Introduction
Metformin is widely used as a first-line glucose-lowering drug;1, 2 however, selection of the most appropriate treatment after metformin failure is poorly established. Sulphonylureas are commonly chosen as add-on treatment because of their rapid effect and low cost.1, 3, 4 Although these drugs can improve the short-term function of β cells, glycaemic control subsequently deteriorates; furthermore, because effects are not glucose-dependent, risk of hypoglycaemia might be increased, which can restrict doses used in clinical practice.5
Glucagon-like peptide (GLP)-1 receptor agonists have become established as treatments for type 2 diabetes.6, 7 They improve glycaemic control, with glucose-dependent stimulation of insulin secretion and no increased risk of hypoglycaemia, and have been associated with weight loss and improvements in biomarkers of cardiovascular risk.8, 9, 10, 11 These drugs have shown protective action in β cells, and findings from clinical trials have noted improved β-cell function,12, 13, 14 thus raising expectations that GLP-1 receptor agonists might delay disease progression.15, 16
We aimed to assess durability of glycaemic control achieved with GLP-1 receptor agonist exenatide twice a day and sulphonylurea glimepiride in patients with type 2 diabetes inadequately controlled by metformin alone.
Section snippets
Study design and participants
We undertook this open-label, randomised controlled European Exenatide (EUREXA) trial at 128 centres in 14 countries (Austria, Czech Republic, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Mexico, Poland, Spain, Switzerland, and the UK) between Sept 5, 2006, and March 29, 2011. The rationale and baseline characteristics of the EUREXA phase 3, multinational study have been described previously.17 Eligible participants had type 2 diabetes; were overweight to obese (body-mass index
Results
Figure 1 shows the trial profile. We randomly assigned 1029 of 1404 screened patients to receive either exenatide or glimepiride as add-on treatment to metformin. The intention-to-treat population consisted of 490 patients in the exenatide group and 487 in the glimepiride group; conclusions from the as-treated population were not different from those from the intention-to-treat analysis and are therefore not presented. Of patients who met the primary endpoint, five of those in the exenatide
Discussion
Our findings show that exenatide twice daily as add-on to metformin reduced worsening of glycaemic control and rate of hypoglycaemia compared with add-on glimepiride in patients with type 2 diabetes inadequately controlled by metformin alone. Furthermore, exenatide was more effective than glimepiride for fasting glucose, glucose excursions after meals, and HbA1c concentration. Overall, safety and tolerability of both drugs was consistent with the known safety profiles. The most frequently
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