A recent phase 3 clinical trial demonstrated that empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, achieved a statistically significant reduction in glycated hemoglobin (HbA1c) when compared with placebo among children aged 10-17 years with type 2 diabetes (T2D) who had previously been treated with metformin or insulin, offering pediatric patients a potential new treatment option to bring the blood sugar under control.¹

The incidence of T2D in children and adolescents worldwide has been increasing over the past 2 decades, coinciding with the rise in the prevalence of childhood obesity.³ When compared with adults, diabetic children and adolescents are more prone to developing cardiovascular diseases (CVDs), including hypertension, dyslipidemia, albuminuria, and increased arterial stiffness.^4,5 In general, these patients usually experience a rapid decline in their glycemic control with the current standard treatment and have a poor long-term treatment outcome.^3,5 Therefore, more treatment options with proven safety and efficacy among this patient population are needed to help them achieve better long-term glycemic control and prevent related complications.⁵ Among the antidiabetic drugs, SGLT2 inhibitors have emerged as a unique class of agents for the treatment of T2D since they have a distinct mode of action that results in glucose excretion in the urine and a consequent decrease in plasma glucose.² Empagliflozin is one of the currently available SGLT2 inhibitors and has been approved for treating T2D in adults.² Notably, empagliflozin is the first molecule in this class that demonstrates a statistically significant reduction in HbA1c in the pediatric population.¹

DINAMO was a double-blinded, randomized, placebo-controlled, phase 3 study that evaluated the safety and efficacy of empagliflozin vs. linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor works by reducing blood sugar by increasing insulin levels, or placebo in children and adolescents aged 10-17 years with T2D.⁶ This study recruited 158 patients aged 10-17 years with an HbA1c level of 6.5%-10.5% who were previously receiving metformin, insulin, or both medicines, or who were treatment-naive or not on an active therapy after metformin withdrawal, from 64 sites in 12 countries.^1,6 Eligible patients were randomized 1:1:1 to receive empagliflozin 10mg, or linagliptin 5mg, or a placebo.⁶ Empagliflozin users who had a week of 12 HbA1c levels of ≥7% were further re-randomized 1:1 to either continue receiving the low-dose empagliflozin 10mg, or up-titrate to a higher empagliflozin dose of 25mg.⁶ After a 26-week treatment period, a 26-week safety extension period was followed, where patients in the placebo group on day 1 were re-randomized to receive empagliflozin 10mg, empagliflozin 25mg, or linagliptin 5mg, with a follow-up visit at week 55.⁶ The primary endpoint was the change in the HbA1c level at week 26, while the secondary endpoints included the changes from baseline to week 26 in fasting plasma glucose, body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP), as well as patients who achieved HbA1c <6.5% or HbA1c <7.0%.⁶

The study results showed that in the group receiving empagliflozin along with other baseline treatments, such as diet, exercise, metformin and/or insulin, HbA1c was significantly reduced by 0.84% compared with placebo at week 26 (95% CI: -1.50 to -0.19; p=0.012), while linagliptin achieved a numerical but non-significant reduction in Hb1Ac of 0.34% (95% CI: -0.99 to 0.30; p=0.29).¹ Empagliflozin was well tolerated by pediatric T2D patients, with a safety profile consistent with previous safety findings among adult patients.¹ The rates of serious adverse events (AEs) were comparable between the empagliflozin arm (2%) and the placebo arm (4%).¹ Hypoglycemia was the most reported AE among patients with active anti-diabetic treatments.¹ No episode of severe hypoglycemia was reported.¹

In summary, the favorable safety findings and high efficacy of empagliflozin demonstrated in the DINAMO trial showed great promise for the drug as the first SGLT2 inhibitor to be used for the treatment of children and adolescents with T2D.