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 type 2 diabetes

Abstract

UNLABELLED: Aims/Introduction: We compared the safety and efficacy of liraglutide vs glibenclamide in patients with poorly controlled (HbA1c, 7.4-10.4%) type 2 diabetes. MATERIALS AND METHODS: Subjects were randomly assigned at a 1:2 ratio to receive 1-year treatment with glibenclamide 1.25-2.5 mg/day or liraglutide 0.9 mg/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 week 52 vs baseline, HbA1c 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 HbA1c < 6.9% was achieved by 22.1 and 8.5% of patients, respectively. Fasting plasma glucose fell from 202.8 and 202.1 mg/dL, respectively, to 145.3 and 156.7 mg/dL, respectively. Mean plasma glucose and mean postprandial plasma glucose increment were lower in the liraglutide group. Mean bodyweight was reduced by -0.8 kg in the liraglutide group and increased by 1.0 kg 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 0.9 mg for 52 weeks 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). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00128.x, 2011).