Dapagliflozin cuts HbA1c in paediatric T2D

Dapagliflozin reduced HbA_1c by 1.03 percentage points more than placebo in children and adolescents with type 2 diabetes (T2D), while saxagliptin showed no significant reduction vs placebo in the phase III T2NOW trial presented at EASD 2023.

Adjusted mean change in HbA_1C was −0.62 percent for dapagliflozin vs +0.41 percent for placebo, a difference of −1.03 percent (95 percent confidence interval [CI], -1.57-0.49; p<0.001).

Statistical significance was achieved in the primary endpoint and secondary endpoints vs placebo at week 26, establishing the role of dapagliflozin in controlling glycaemia in children and adolescents with T2D. Additionally, the safety results in this paediatric cohort were consistent with the known safety profile of dapagliflozin in adults with T2D.

“The significant decrease in HbA_1C with dapagliflozin may indicate a reduction in disease progression and its complications,” said study author Dr Naim Shehadeh, professor of endocrinology, Rambam Health Care Campus, Haifa, Israel. “This is an important treatment consideration as children and adolescents with T2D often experience earlier onset of complications and faster disease progression than adults with the same condition.”

Limited treatment options

Despite the increasing burden of T2D globally, treatment options remain limited for children and adolescents. “Some patients find injectable therapies challenging, making the need for effective oral treatment alternatives paramount,” said Ruud Dobber, executive vice president, BioPharmaceuticals Business Unit, AstraZeneca.

T2NOW was a 26-week trial with a 26-week extension. Patients were 10–17 years of age with uncontrolled T2D (HbA_1C 6.5 –10.5 percent) who were already receiving metformin, insulin, or both medications. They were randomly assigned in a 1:1:1 ratio to dapagliflozin 5 mg (n=81), saxagliptin 2.5 mg (n=88), or placebo (n=76). [NEJM Evid 2023;doi:10.1056/EVIDoa2300210]

Those in the active treatment groups, with HbA_1C of ≥7 percent at week 12, were further randomized at week 14 to continue with their current dose or uptitrate to a higher dose (dapagliflozin 10 mg or saxagliptin 5 mg). The primary endpoint was change in HbA_1C at week 26. Safety was assessed over 52 weeks.

HbA_1c difference at week 26

The difference with placebo in adjusted mean change in HbA_1C at week 26 was −1.03 percentage points (95 percent confidence interval [CI], −1.57 to −0.49; p<0.001) for dapagliflozin and −0.44 percentage points (95 percent CI, −0.93 to 0.05; p=0.078) for saxagliptin.

Adverse events (AEs) and serious AEs occurred in 72.8 percent and 8.6 percent of patients receiving dapagliflozin, 69.3 percent and 8.0 percent of those receiving saxagliptin, and 71.1 percent and 6.6 percent of patients receiving placebo. Severe hypoglycaemia occurred in 4.9 percent, 4.5 percent, and 7.9 percent of patients in each group, respectively.

Over 52 weeks, the most common AE reported was headache (dapagliflozin 14.8 percent, placebo 5.3 percent), with most events only mild.

Dapagliflozin, but not saxagliptin, showed significant improvement in HbA_1C vs placebo. Indicated as an adjunct treatment to help improve glycaemic control in T2D, dapagliflozin is also approved in over 100 countries for heart failure with reduced ejection fraction and chronic kidney disease.