Exenatide 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
The Lancet, 07/03/2012
Gallwitz B et al. – The findings provide evidence for the benefits of exenatide versus glimepiride for control of glycaemic deterioration in patients with type–2 diabetes inadequately controlled by metformin alone.Methods
- The authors did an open-label, randomised controlled trial at 128 centres in 14 countries between Sept 5, 2006, and March 29, 2011.
- Patients aged 18—85 years with type 2 diabetes inadequately treated by metformin were randomly assigned via a computer-generated randomisation sequence to receive exenatide twice daily or glimepiride once daily as add-on to metformin.
- Randomisation was stratified by predetermined categories of glycated haemoglobin (HbA1C) concentration.
- The primary outcome was time to inadequate glycaemic control and need for alternative treatment, defined as an HbA1c concentration of more than 9% after the first 3 months of treatment, or more than 7% at two consecutive visits after the first 6 months.
- Analysis was by intention to treat.
- They randomly assigned 515 patients to the exenatide group and 514 to the glimepiride group, of whom 490 versus 487 were the intention-to-treat population. 203 (41%) patients had treatment failure in the exenatide group compared with 262 (54%) in the glimepiride group (risk difference 12.4 [95% CI 6.2—18.6], hazard ratio 0.748 [0.623—0.899]; p=0.002). 218 (44%) of 490 patients in the exenatide group, and 150 (31%) of 487 in the glimepiride group achieved an HbA1c concentration of less than 7% (p<0.0001), and 140 (29%) versus 87 (18%) achieved concentrations of 6.5% and less (p=0.0001).
- They noted a significantly greater decrease in bodyweight in patients given exenatide than in those given glimepiride (p<0.0001).
- Five patients in each treatment group died from causes unrelated to treatment.
- Significantly fewer patients in the exenatide group than in the glimepiride group reported documented symptomatic (p<0.0001), nocturnal (p=0.007), and non-nocturnal (p<0.0001) hypoglycaemia.
- Discontinuation because of adverse events (mainly gastrointestinal) was significantly higher (p=0.0005) in the exenatide group than in the glimepiride group in the first 6 months of treatment, but not thereafter.