Update: Pediatric Diabetes

Abstract

Despite the marked rise in incidence of type 2 diabetes (T2D) in adolescents and young adults, metformin remained the only US Food and Drug Administration (FDA) approved oral medication for treatment of early disease in this population. Multiple groups of medications are available for adults with T2D. Loss of glycemic control has been a major drawback with metformin monotherapy which eventually requires addition of insulin. For the first time in July 2019, the FDA approved the glucagon-like peptide 1 (GLP-1) receptor agonist, liraglutide, for pediatric use. A study published in the New England Journal of Medicine in their August 2019 edition titled “Liraglutide in Children and Adolescents with Type 2 Diabetes” laid the foundation for this FDA recognition. The Evaluation of Liraglutide in Pediatrics with Diabetes (Ellipse) phase 3 randomized control trial was conducted at 84 sites in 25 countries from 2012 to 2018. The aim of the study was to assess the superiority of liraglutide compared to placebo when added to metformin therapy with or without insulin use in adolescents with T2D between 10 and 17 years of age. Patients were randomly assigned to receive subcutaneous liraglutide (up to 1.8 mg per day) (n = 66) or placebo (n = 68) for a 26-week double-blind period in a 1:1 ratio, followed by a 26-week open-label extension period. At the 26-week initial analysis of the primary efficacy end point, the mean glycosylated hemoglobin level had decreased significantly by 0.64 percentage points with liraglutide and increased by 0.42 percentage points with placebo (P < .001); the difference increased to −1.30 percentage points by 52 weeks indicating the superiority of liraglutide to placebo. The fasting plasma glucose level had decreased at both time points in the liraglutide group but had increased in the placebo group. The most common adverse effects associated with liraglutide in this trial were mild gastrointestinal complaints. Interestingly, despite an improvement in the diabetes profile, this study did not see a significant change in the body mass index (BMI) between the two groups. They attribute this to the possibility of children continuing to grow as well as the small sample size. GLP-1 receptor agonists have been in use in adults since 2005 and have shown effectiveness in improving glycemic control and having cardioprotective ability. They also help with weight reduction in adults. In August 2019, a review was published on the first oral GLP-1 agonist, semaglutide, in Diabetes Technology & Therapeutics. We hope that more studies are performed on pediatric T2D populations to help them achieve better glycemic control. We owe our patients more medication options than just metformin and insulin. This makes the Ellipse trial so important, and liraglutide in conjunction with metformin (with or without insulin) is a good additional option for adolescents with T2D. DOI: 10.1111/1753-0407.13012