medwireNews: The randomised Ellipse trial has demonstrated significant blood glucose reductions with the glucagon-like peptide-1 receptor agonist liraglutide in children and adolescents with type 2 diabetes already taking metformin.
During 26 weeks of treatment, average glycated haemoglobin (HbA1c) levels fell by 0.64 percentage points from a baseline of 7.87% (63 mmol/mol) in the 66 children, aged 10 to less than 17 years, who were randomly assigned to receive liraglutide (subcutaneous injection, once daily).
By contrast, average HbA1c in the 68 children receiving placebo injections increased by 0.42 percentage points from a baseline of 7.69% (61 mmol/mol), giving an estimated treatment difference of 1.06 percentage points in favour of liraglutide.
Speaking to medwireNews, study author William Tamborlane (Yale University, New Haven, Connecticut, USA) described the trial as “transformational”.
He stressed that the only medication currently approved by the regulatory agencies as an add-on therapy after metformin failure is insulin, “and insulin does not do well in this population”.
“That’s why this is such an important study: it’s the first successful trial that is required for the regulatory agencies to approve an additional new drug for treatment of kids with type 2 – this is the first one since metformin.”
As reported in The New England Journal of Medicine, the trial participants had been diagnosed with type 2 diabetes an average of 1.9 years previously. All were using metformin, titrated to the maximum tolerated dose during an 11- to 12-week run-in period, and 18.7% were using insulin.
Liraglutide also significantly reduced fasting glucose levels relative to placebo, and significantly more participants achieved their HbA1c target of 7.0% (53 mmol/mol) or lower, at 63.7% versus 36.5%. The treatment difference in HbA1c levels in favour of liraglutide increased further during an additional 26 weeks of open-label treatment, to 1.30 percentage points.
The average baseline BMI standard deviation score (SDS) was 3.03 in the liraglutide group and 2.86 in the placebo group. During the blinded phase of the trial this decreased in both groups, by a respective 0.25 and 0.21, but the difference between the two did not attain statistical significance, despite the known weight-reducing effects of liraglutide in adults with diabetes.
Tamborlane believes that slow liraglutide dose titration might explain this finding. All participants in the liraglutide group started on a dose of 0.6 mg/day, increasing to 1.2 mg/day and then 1.8 mg/day (the adult dose) if needed, but only 53.6% were on the highest dose by week 48, with 28.6% achieving glucose control on the lowest dose. Weight loss with liraglutide is dose-dependent; the approved dose specifically for weight loss in adults is 3.0 mg/day.
“So it may have been that for caution dealing with kids they didn’t push on to the highest dose, which is the standard in adults, and that may explain why they did not have as much weight loss”, said Tamborlane.
The only adverse effects to occur significantly more often in the liraglutide than placebo groups were gastrointestinal events, specifically nausea and vomiting (28.8 vs 13.2 and 25.8 vs 8.8%, respectively), but Tamborlane described these as “relatively early and relatively mild, and very similar to what you would see when we start someone on metformin.”
Hypoglycaemia was also significantly more frequent with liraglutide than placebo (45.5 vs 25.0%), but there were no severe episodes.
By Eleanor McDermid
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
N Engl J Med 2019; doi:10.1056/NEJMoa1903822