The US Food and Drug Administration (FDA) has extended the indication for the glucose-lowering drug liraglutide (Victoza, Novo Nordisk) to include patients as young as 10 years of age, making it the first noninsulin drug approved for treating pediatric type 2 diabetes in almost 20 years. Liraglutide, a subcutaneous injectable glucagonlike peptide–1 receptor agonist, has been available for treating adults with type 2 diabetes since 2010. It is the first drug other than insulin to be approved specifically for treating youth with type 2 diabetes since metformin was approved for pediatric use in 2000. Although type 2 diabetes was previously considered a condition primarily of older adults, incidence has been increasing in young adults and children. More than 5000 new cases are diagnosed in the United States each year among those younger than 20 years, according to data from the Centers for Disease Control and Prevention, as reported in an FDA announcement about the new indication. The new approval was based on data from the Efficacy and Safety of Liraglutide in Combination With Metformin Compared to Metformin Alone, in Children and Adolescents With Type 2 Diabetes (ELLIPSE) trial. That trial was presented in April 2019 at the Pediatric Academic Societies 2019 Meeting and was simultaneously published online in the New England Journal of Medicine. Among 135 obese patients aged 10 to 17 years who had type 2 diabetes that was inadequately controlled with diet and exercise, metformin, and/or insulin, those treated with liraglutuide experienced a drop of 0.64 percentage points in HbA1c compared to patients who received placebo, for whom HbA1c levels increased 0.42 percentage points (P < .001). More patients in the liraglutide group achieved an HbA1c level <7% (64% vs 38%; P < .001), and the differences remained significant at 52 weeks. At the time, ELLIPSE lead investigator William V. Tamborlane, MD, of Yale University, New Haven, Connecticut, told Medscape Medical Newsthat the study was "practice changing" because "metformin fails quickly as monotherapy in type 2 diabetes kids, and insulin is the only second-line drug approved for kids with type 2 diabetes." The approval comes at a time when physicians are expressing alarm about the impact of pediatric type 2 diabetes. At the recent American Diabetes Association (ADA) 2019 Scientific Sessions, results were presented from two major trials, Restoring Insulin Secretion (RISE) and Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY-2), that underscored the problem. In RISE, adults with prediabetes or new-onset diabetes who received treatment experienced improvements in beta-cell function during the year of the study compared with those who received placebo. Those findings contrasted with data presented at the 2018 ADA meeting regarding adolescents. In those patients, early treatment for a year with metformin or insulin failed to prevent deterioration in beta-cell function. In TODAY-2, which involved more than 500 patients diagnosed with type 2 diabetes during their early teens, an alarmingly high rate of diabetes-associated complications had arisen by the time the patients were in their mid-20s. These complications included cardiovascular events and pregnancy complications. In August 2017, the FDA granted liraglutide a labeling indication for reducing the risk for myocardial infarction, stroke, and cardiovascular death in adults with type 2 diabetes who have established cardiovascular disease. Whether the drug can prevent cardiovascular events in youth with type 2 diabetes is not known. Liraglutide's label also includes a boxed warning about the increased risk for thyroid C-cell tumors, as well as warnings about pancreatitis, pen sharing, hypoglycemia when used in conjunction with insulin or sulfonylureas, renal impairment or kidney failure, hypersensitivity, and acute gallbladder disease. The most common side effects are nausea, diarrhea, vomiting, decreased appetite, indigestion, and constipation. "The FDA encourages drugs to be made available to the widest number of patients possible when there is evidence of safety and efficacy," said Lisa Yanoff, MD, acting director of the Division of Metabolism and Endocrinology Products in the FDA's Center for Drug Evaluation and Research. "Victoza has now been shown to improve blood sugar control in pediatric patients with type 2 diabetes. The expanded indication provides an additional treatment option at a time when an increasing number of children are being diagnosed with this disease," she said. Source
