A randomized trial to investigate the efficacy and safety of once-daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg.

AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001). Liraglutide 1.8 mg was associated with significantly greater odds of participants reaching HbA1c <7.0% (estimated odds ratio [EOR] 3.87; 95% CI 2.12, 7.08; P < 0.0001) and ≤6.5% (EOR 3.78; 95% CI 1.36, 10.54; P = 0.0109) compared with 0.9 mg. Both doses were well tolerated. CONCLUSIONS: Liraglutide 1.8 mg had better efficacy in improving HbA1c levels after 26 weeks treatment vs 0.9 mg in Japanese patients, with both doses well tolerated.

Effect of liraglutide treatment on body mass index and weight parameters in children and adolescents with type 2 diabetes: Post hoc analysis of the ellipse trial.

BACKGROUND: Weight loss in children and adolescents with type 2 diabetes (T2D) is associated with improved glycaemic control. OBJECTIVES: To assess the effects of liraglutide vs placebo on body mass index (BMI) and weight parameters in children and adolescents with T2D using data from the ellipse trial (NCT01541215). METHODS: The ellipse trial randomized participants (10-<17 years old, BMI >85th percentile, T2D, glycated haemoglobin [HbA1c ] 7.0%-11.0% [if diet- and exercise-treated] or 6.5% to 11.0% [if treated with metformin, basal insulin or both]) to liraglutide or placebo. This post-hoc analysis evaluated changes from baseline to weeks 26 and 52 in absolute BMI, percent change in BMI and other weight-related parameters. Changes were assessed by liraglutide overall (all doses) and liraglutide by dose (0.6, 1.2 and 1.8 mg/day) vs placebo using a pattern mixture model of observed data, with missing observations imputed from each treatment group. RESULTS: In total, 134 participants were included. There were statistically significant differences between groups in certain parameters, including absolute BMI (estimated treatment difference [ETD] -0.89 kg/m2 ; 95% confidence interval [CI] -1.71,-0.06) and percent change in BMI (ETD -2.73%; 95% CI -5.15,-0.30) at week 52, but none at week 26. Dose-dependent effects were not observed for liraglutide vs placebo for all BMI/weight parameters. CONCLUSIONS: Compared with placebo, liraglutide was associated with statistically significant reductions in BMI/weight parameters at week 52, but not week 26, in children and adolescents with T2D.