EUREXA: Exenatide vs Glimepiride for Prevention of Glycemic Deterioration Among Those with Type 2 Diabetes and Metformin Failure

Gallwitz B, Guzman J, Dotta F, et al. 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. Lancet. 2012;379(9833):2270-2278. 

Burton E. Sobel, MD, provides expert commentary on EUREXA. Click here.

The European Exenatide (EUREXA) trial is an open-label, randomized, controlled trial comparing add-on exenatide with glimepiride for durability of glycemic control among subjects with type 2 diabetes that is inadequately controlled with metformin monotherapy.  

Subjects (aged 18-85 years, poorly controlled type 2 diabetes [A1C ≥6.5% and <9%], BMI ≥25 to <40 kg/m2) were randomized to exenatide bid (n=490) or glimepiride qd (n=487), both as add-on therapy to metformin, and were stratified by A1C into the following groups: ≤7.3%; >7.3% to <8.2% and less; and >8.2%. At baseline, diabetes duration was 5.8 years in the exenatide group and 5.5 years in the glimepiride group; A1C levels were 7.5% and 7.4%, respectively. The primary outcome was time to inadequate glycemic control, defined as A1C >9% after the first 3 months of study treatment, or >7% at two consecutive study visits 3 months apart after the first 6 months.  

Results over average treatment time of ~2 years:  

  • Mean exenatide dose was 17.35 µg/day; mean glimepiride dose was 2.01 mg/day.  
  • Over average treatment time of ~2 years, 41% (n=203) of exenatide-treated subjects had treatment failure vs 54% (n=262) of those in the glimepiride group (risk difference, 12.4%, 95% CI, 6.2-18.6; hazard ratio, 0.748 (95% CI, 0.623–0.899; P=0.002).  
  • Exenatide was more effective as add-on treatment for patients with metformin failure compared with glimepiride (95% CI, 0.623 to 0.899; P=0.002).  
  • Time to treatment failure was longer among exenatide-treated subjects vs those treated with glimepiride (180 weeks vs 142 weeks, respectively; P=0.032).  
  • Exenatide was associated with lower A1C levels over time vs glimepiride. A greater number of subjects treated with exenatide achieved A1C <7.0% and ≤6.5% vs those in the glimepiride group
    • A1C <7%: 45% (218) of exenatide-treated subjects vs 31% (150) of glimepiride-treated subjects; P<0.0001  
    • A1C ≤6.5%: 29% (140) of those in the exenatide group vs 18% (87) of those in the glimepiride group; P=0.0001  
  • More exenatide-treated subjects discontinued treatment due to adverse events (mainly gastrointestinal) over the first 6 months of treatment, but not thereafter.  
  • The proportion of subjects reporting hypoglycemia was lower with exenatide vs glimepiride (P<0.001).
    • At least 1 hypoglycemic episode reported: 36% of those in the exenatide group vs 67% in the glimepiride group (P<0.0001)  
    • Hypoglycemia frequency (least-squares mean): 1.52 episodes/year with exenatide (95% CI, 1.26–1.82) vs 5.32 episodes/year with glimepiride (95% CI, 4.47–6.34)  


July 2012 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest. 

Related content: 

OnsiteInsight® eNewsletter: ADA 2012 

EUREXA Trial: Design 

EUREXA Trial: Design and Enrollment Profile 

EUREXA Trial: Primary Outcome—Time to Treatment Failure 

EUREXA Trial: Attainment of A1C <7.0% and ≤6.5% 

EUREXA Trial: Hypoglycemia and Adverse Events 

EUREXA Trial: Change in Body Weight  

Last Modified: 3/17/2014