ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: N Engl J Med. 2019;381(7):637–46. doi: 10.1056/NEJMoa1903822

Short summary: Liraglutide is superior to placebo in improving glycaemic control in children and adolescents with T2DM.

Comment: Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, also known as an incretin mimetic. It causes glucose-dependent stimulation of insulin secretion, inhibits glucagon release, delays gastric emptying and suppresses appetite. Liraglutide was approved for adults with T2DM one decade ago. This industry-funded, international, multicenter, randomized, controlled, phase III trial (the Ellipse study) studied the safety and effectiveness of Liraglutide in children and adolescents with T2DM.

In total, 135 children with T2DM (aged 10–17 years), treated with diet, metformin or insulin, were randomized to receive either subcutaneous liraglutide (escalating dose from 0.6 to 1.8 mg per day) or placebo. After 26 weeks, the mean glycated haemoglobin (HbA1c) level decreased by 0.64% in the liraglutide group, but increased by 0.42% in the placebo group; after 52 weeks, this difference was even greater (−0.50% vs. 0.80%). Furthermore, a higher proportion of adolescents achieved an HbA1c <7% on liraglutide vs. placebo (63.7% vs, 36.5%; P <0.001). BMI-Z score did not differ between the groups (please see also paper 11.12); the authors hypothesized that this might be because only ~50% of the liraglutide group received the full dose of 1.8 mg per day during the trial (per study protocol, doses were not increased if the average of fasting plasma glucose measurements on 3 consecutive days preceding the dose-escalation visit was <110 mg/dl or 6.1 mmol/l). Gastrointestinal complaints and hypoglycaemic events were more common in the liraglutide group.

Clinicians should be aware that liraglutide is available in our tool-box for management of children and adolescents with T2DM.