According to the FDA, the approvals “provide a new class of medicines taken by mouth to treat pediatric T2D.”
The FDA has approved empagliflozin (Jardiance; Boehringer Ingelheim and Eli Lilly and Company) and empagliflozin plus metformin hydrochloride (Synjardy; Boehringer Ingelheim) to aid diet and exercise in improving blood sugar control for children 10 years and up with type 2 diabetes (T2D), according to a press release from the federal agency.1 Empagliflozin, the active ingredient in both approvals, “works by increasing the excretion of glucose in the urine.”
A supplemental New Drug Application (sNDA) for empagliflozin was accepted by the FDA in March 2023, and received a Priority Review Designation for the approval. The sNDA and approval follow positive results in which empagliflozin demonstrated safety and efficacy in the DINAMO (NCT03429543) phase 3 trial, which enrolled 157 patients aged 10 to 17 years with inadequately controlled T2D.
For 26 weeks, patients were randomly assigned 1 of 3 treatment arms; empagliflozin, linagliptin (Tradjenta; Boehringer Ingelheim Pharmaceuticals), or placebo. Fifty-two patients were treated with empagliflozin and experienced a 0.2% (on average) decrease in hemoglobin A1c. In comparison, an average 0.7% increase in hemoglobin A1c was observed in 53 patients in a placebo group. Reductions in fasting plasma glucose was also observed in patients that took empagliflozin.
According to the FDA, the approvals “provide a new class of medicines taken by mouth to treat pediatric T2D.” The only other oral therapy for T2D in children is metformin, first approved for pediatric use in 2000.
“Compared to adults, children with type 2 diabetes have limited treatment options, even though the disease and symptom onset generally progress more rapidly in children,” said Michelle Carey, MD, MPH, associate director for therapeutic review, Division of Diabetes, Lipid Disorders, Obesity, FDA’s Center for Drug Evaluation and Research. “[The] approvals provide much-needed additional treatment options for children with type 2 diabetes.”
For children treated with empagliflozin, common side effects were similar to those reported in adults. A higher risk of hypoglycemia was reported among pediatric patients in the newly-approved indication compared to placebo, “regardless of whether they were taking other therapies for diabetes,” according to the FDA. The most common side effects in empagliflozin-treated adults included urinary tract infections and female fungal infections. Diarrhea, nausea, and upset stomach were the most common side effects for patients treated with metformin. Due to an increased risk of diabetic ketoacidosis, empagliflozin and empagliflozin plus metformin hydrochloride are not recommended in patients with type 1 diabetes (T1D). Further, according to the FDA, “Jardiance and Synjardy are also not recommended for use to improve blood sugar control in patients with severe kidney problems and should not be used in patients who previously have had a serious allergic reaction to them.” Empagliflozin plus metformin hydrochloride “must not” be used in metabolic acidosis or diabetic ketoacidosis patients, the FDA states.
Empagliflozin was FDA-approved in 2014 to improve blood sugar control as an aid to diet and exercise for adults with T2D. In adults with T2D, empagliflozin is also approved to reduce the risk of cardiovascular death and established cardiovascular disease. It is also designed to reduce the risk of cardiovascular death and heart failure-related hospitalization in adults with heart failure.
In 2015, the FDA approved empagliflozin plus metformin hydrochloride as an addition to diet and exercise aimed to improve glucose control in adult T2D patients. According to the FDA, “Empagliflozin, when used as a component of Synjardy, is approved 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.”