Fifty-two-week, randomized, multicenter trial to compare the safety and efficacy of the novel glucagon-like peptide-1 analog liraglutide vs glibenclamide in patients with type2 diabetes

Abstract

Aims/Introduction: We compared the safety and efficacy of liraglutide vs glibenclamide in patients with poorly controlled (HbA 1c, 7.4-10.4%) type2 diabetes. Materials and Methods: Subjects were randomly assigned at a 1:2 ratio to receive 1-year treatment with glibenclamide 1.25-2.5mg/day or liraglutide 0.9mg/day. Other oral anti-diabetic drugs (OAD) were prohibited during the trial. Adverse events (AE) were monitored. Results: A total of 400 patients (liraglutide group, n=268; glibenclamide group, n=132) were randomized and exposed to trial products. At week52 vs baseline, HbA 1c in the liraglutide and glibenclamide groups was reduced from 9.3 to 7.8% and from 9.2 to 8.2%, respectively. Treatment difference (liraglutide-glibenclamide) at the end of the study was -0.49 (95% CI, -0.71 to -0.27). In the liraglutide and glibenclamide groups, Japan Diabetes Society target HbA 1c<6.9% was achieved by 22.1 and 8.5% of patients, respectively. Fasting plasma glucose fell from 202.8 and 202.1mg/dL, respectively, to 145.3 and 156.7mg/dL, respectively. Mean plasma glucose and mean postprandial plasma glucose increment were lower in the liraglutide group. Mean bodyweight was reduced by -0.8kg in the liraglutide group and increased by 1.0kg in the glibenclamide group. The proportion of patients reporting at least one treatment-emergent AE (TEAE) in the liraglutide and glibenclamide groups was 91.4 and 91.7%, respectively. Most TEAE were mild in severity. No major hypoglycemic episode was observed. Conclusions: Once-daily administration of liraglutide 0.9mg for 52weeks provides more favorable metabolic control and safety profile compared with glibenclamide. Patients on liraglutide lost bodyweight, whereas those on glibenclamide gained weight. This trial was registered with ClinicalTrial.gov (no. NCT00393718). © 2011 Asian Association for the Study of Diabetes and Blackwell Publishing Asia Pty Ltd.