The US Food and Drug Administration (FDA) approved Jardiance (empagliflozin) and Synjardy (empagliflozin and metformin hydrochloride) for addition to diet and exercise to improve control of blood sugar in children 10 years and older with type 2 diabetes.
These endorsements provide a new class of oral medications to treat pediatric type 2 diabetes. Metformin, the only other oral therapy available for kids with the disease, was first approved for pediatric use in 2000.
“Compared to adults, children with type 2 diabetes have few treatment options, although disease onset and symptoms often progress more rapidly in them,” said Dr. Michelle Carey, associate director of therapeutic review for the Division of Diabetes, Lipids and Obesity at the FDA’s Center for Drug Evaluation and Research. “Today’s approvals provide much-needed additional treatment options for children with type 2 diabetes,” she added.
Type 2 diabetes - the most common form of diabetes - is a chronic, progressive condition in which the body does not produce or use insulin normally, leading to high levels of glucose (sugar) in the blood. According to data from the SEARCH for Diabetes in Youth study, the incidence of type 2 diabetes in children increased 4.8% per year between 2002 and 2015 and is expected to continue to increase. As of 2017, there were approximately 28,000 cases of type 2 diabetes in children in the US. If current trends continue, by 2060 that number is expected to be approximately 220,000, with most cases occurring in minority ethnic groups, such as non-Hispanic black people and Hispanics.
Empagliflozin, the active ingredient in Jardiance and Synjardy, works by increasing the excretion of glucose in the urine. Synjardy also contains metformin.
The safety and effectiveness of empagliflozin in children was studied in a double-blind, randomized, placebo-controlled trial. 157 patients aged 10 to 17 years with inadequately controlled type 2 diabetes participated. Members were randomly assigned to one of three treatment arms for 26 weeks: empagliflozin, a DPP-4 inhibitor (linagliptin), or placebo.
At the start of the trial, 51% of patients were taking metformin alone, 40% were treated with a combination of metformin and insulin, 3% were treated with insulin alone, and 6% of patients were not taking other diabetes medications. .
The trial found that, at week 26, empagliflozin treatment was superior in reducing hemoglobin A1c, a measure of average blood sugar, compared to placebo. The 52 patients treated with empagliflozin had an average 0.2% decrease in hemoglobin A1c compared to an average 0.7% increase in hemoglobin A1c in the 53 patients taking placebo, representing a decrease of 0.2%. 8% in hemoglobin A1c with empagliflozin compared to placebo. Patients treated with empagliflozin also had reductions in fasting plasma glucose, a measure of blood sugar taken after not eating or drinking for at least eight hours, compared to patients taking placebo.
Common adverse events in children treated with empagliflozin were similar to those reported in adults, except that there was an increased risk of hypoglycemia (low blood sugar) among pediatric patients 10 years and older taking empagliflozin compared to placebo, regardless of whether they were taking other diabetes therapies.
The most common side effects in adults treated with empagliflozin include urinary tract infections and female fungal infections. While the most common adverse reactions in patients treated with metformin are diarrhea, nausea and stomach upset.
Jardiance and Synjardy are not recommended in patients with type 1 diabetes due to an increased risk of diabetic ketoacidosis. They are also not suggested to improve blood sugar control in patients with severe kidney problems and should not be used in people who have previously had a severe allergic reaction to them. Synjardy should not be used in patients with metabolic acidosis or diabetic ketoacidosis (increased ketones in the blood or urine). For additional information on the risks associated with Jardiance and Synjardy, the prescribing information should be consulted.
Jardiance was originally approved by the FDA in 2014 as an adjunct to diet and exercise to improve blood sugar control in adults with type 2 diabetes. It is also supported to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease, and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure.
Synjardy was originally approved by the FDA in 2015 as an adjunct to diet and exercise to improve glucose control in adults with type 2 diabetes. Empagliflozin, when used as a component of Synjardy, is approved to reduce the risk of death cardiovascular in adults with type 2 diabetes and established cardiovascular disease and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure.
Jardiance and Synjardy received priority review designations for today’s approvals. A priority review designation directs overall attention and resources to the evaluation of drug applications that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions.
The FDA granted approvals for Jardiance and Synjardy to Boehringer Ingelheim.
