Ellipse trial opens Victoza to children aged 10 and older

The New England Journal of Medicine published results from the Ellipse trial, the first large randomized test of a GLP-1 receptor agonist in children and teenagers with type 2 diabetes. Daily injected liraglutide, added on top of metformin, improved blood sugar control over 52 weeks compared with placebo, but caused more stomach-related side effects ^[1].

What the trial tested

Researchers enrolled patients aged 10 to less than 17 years and randomly assigned them 1:1 to subcutaneous liraglutide at up to 1.8 mg per day or to placebo for a 26-week double-blind period, followed by a 26-week open-label extension ^[1]. Everyone in the trial took metformin, and some also used basal insulin ^[1].

To qualify, participants had to have a body-mass index above the 85th percentile, plus an A1C between 7.0% and 11.0% if they were managing diabetes with diet and exercise alone, or between 6.5% and 11.0% if they were already on metformin with or without insulin ^[1].

Of 135 patients randomized, 134 received at least one dose: 66 on liraglutide and 68 on placebo ^[1]. The two groups looked similar at the start, with a mean age of 14.6 years ^[1]. The study was funded by Novo Nordisk and is registered as NCT01541215 ^[1].

The numbers

At the 26-week primary analysis, average A1C fell by 0.64 percentage points in the liraglutide group and rose by 0.42 percentage points in the placebo group ^[1]. That works out to an estimated treatment difference of 1.06 percentage points in favor of liraglutide, with a P value below 0.001 ^[1]. By 52 weeks, the gap between the groups had widened to 1.30 percentage points ^[1].

Fasting plasma glucose, a secondary endpoint, dropped at both time points in the liraglutide group and rose in the placebo group ^[1].

On safety, the share of patients reporting any adverse event was similar: 56 patients (84.8%) on liraglutide and 55 (80.9%) on placebo ^[1]. But the overall rates of adverse events, and of gastrointestinal adverse events specifically, were higher with liraglutide ^[1]. The authors concluded that liraglutide up to 1.8 mg per day, added to metformin with or without basal insulin, improved glycemic control over 52 weeks, and that this efficacy "came at the cost of an increased frequency of gastrointestinal adverse events" ^[1].

Why it matters for patients

The trial's stated starting point is that metformin is the approved first-choice treatment for most young people with type 2 diabetes, but that early loss of blood sugar control has been seen with metformin alone ^[1]. Before this study, whether adding liraglutide was safe and effective in youth was unknown ^[1].

One detail worth noting for families: placebo patients did not simply stay flat. Their A1C went up an average of 0.42 percentage points over 26 weeks even while taking metformin, which is part of why the difference between groups looks as large as it does ^[1].

The trade-off is spelled out in the results. Nearly the same proportion of kids in each group reported at least one adverse event, but nausea-type gastrointestinal problems were more common on the active drug ^[1]. That pattern is the kind of thing clinicians and families weigh together.

This trial studied liraglutide, an older daily-injection GLP-1 drug, not semaglutide or tirzepatide. The published abstract does not address regulatory approvals, labeling, cost or insurance coverage, so how these results translate into US prescribing is not covered by this source.

What happens next

The 52-week trial, including the 26-week open-label extension, was complete at publication ^[1]. The paper appeared in the New England Journal of Medicine in 2019, with copyright held by the Massachusetts Medical Society ^[1]. A letter commenting on the results, "Liraglutide in Children and Teens with Type 2 Diabetes," was published in the same journal on October 31, 2019 ^[1]. Longer-term outcomes beyond 52 weeks are not reported in this source.