Summary: In a double-blind, randomized, phase 3 trial, 135 overweight and obese adolescents, aged 10 to 17 years with T2DM, were randomly assigned to receive subcutaneous liraglutide (up to 1.8 mg per day) or placebo, both in addition to metformin treatment. At the 26-week analysis, mean HbA1c decreased by 0.64 percentage points with liraglutide and increased by 0.42 percentage points with the placebo, resulting in a −1.06 percentage point difference (P<0.001); the difference increased to −1.30 percentage points by 52 weeks.
Comment: Despite the evidence that the disease course of T2DM is more aggressive among adolescents than adults, treatment options for adolescents are limited. Liraglutide (marketed as Saxenda® and Victoza®), a human glucagon-like peptide-1 (GLP-1) receptor agonist, was approved one decade ago to treat adults with T2DM with insufficient glycemic control. In addition, the FDA approved liraglutide injection for chronic weight management in individuals with obesity or overweight and a weight-related comorbid condition, based on clinical trials that repeatedly demonstrated the ability of GLP-1 receptor agonists to induce weight loss.1 Appetite suppression and delayed gastric emptying are thought to be responsible for the weight lowering effects of GLP-1.
In the current study, liraglutide 1.8 mg injection showed superiority to placebo in decreasing HbA1c levels among adolescents; a significantly higher proportion of children and adolescents treated with liraglutide (63.7%) achieved HbA1C <7% at week 26 than did those treated with placebo (36.5%). Of note, there was no difference in weight loss between the two adolescent groups, despite the known weight-reducing effects of liraglutide in adults with or without diabetes. This is possibly because only about 50% of the adolescents received the approved dose for weight loss in adults, 3.0 mg/day.
The results of this ELLIPSE trial have been submitted to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for evaluation of liraglutide as a potential treatment option for children aged 10 years and above with T2DM.
Reference: 1. Mehta A, Marso SP, Neeland IJ. Liraglutide for weight management: a critical review of the evidence. Obes Sci Pract. 2016; 3(1): 314.