A clinical trial evaluating dapagliflozin as an adjunct to insulin therapy has demonstrated significant improvements in kidney function and glycemic control for adolescents with type 1 diabetes (T1D). The multicenter, double-blinded, randomized, placebo-controlled study (NCT04333823) enrolled 98 patients under 19 years old and found that combination therapy reduced chronic kidney disease risk while improving overall health outcomes.
Study Design and Patient Population
The ATTEMPT study was conducted across three sites over a 16-week period, with 53% of participants being female. Patients received either dapagliflozin 5 mg or placebo alongside their standard insulin treatment. The primary endpoint focused on measured glomerular filtration rate (GFR), while secondary outcomes included glycated hemoglobin A1c, adverse events, diabetic ketoacidosis, hypoglycemic events, urinary and genitourinary tract infections, glycemic variability, weight, body mass index, and total daily insulin dose.
"Our findings showed that adolescents who received this combination therapy were able to improve many symptoms typically associated with insulin-managed type one diabetes," said Dr. Farid Mahmud, physician at The Hospital for Sick Children and lead investigator. "This could inform a new early intervention strategy for the growing population of teenagers with type one diabetes."
Significant Clinical Improvements
The trial demonstrated substantial benefits across multiple parameters. Dapagliflozin reduced measured GFR by 8.8 ml min⁻¹ 1.73 m⁻² compared with placebo, with patients having higher baseline measured GFR showing greater attenuation when treated with the drug. HbA1c levels decreased by 0.47%, and time in range increased by 9%. Additionally, participants experienced a 2.8 kg reduction in body weight.
The safety profile remained favorable, with adverse events similar between groups and only one mild case of diabetic ketoacidosis reported in the study drug group. Investigators concluded that "in youth with T1D, dapagliflozin as an adjunct-to-insulin treatment reduced mGFR, improved glycemic control, and was safe when combined with ketone testing and risk mitigation strategies."
Addressing Research Gaps in Adolescent Care
The research team specifically focused on adolescents, a population often underrepresented in clinical trials despite facing unique challenges. Hormonal changes, psychological development, and shared responsibility between teens and parents for managing treatment protocols create barriers to research participation in this age group.
Previous data had shown similar results in adults, but the investigators recognized the need for age-specific evidence. The study incorporated patient partner involvement, with Lynne McArthur providing feedback on trial design and recruitment materials based on her experience as a parent of twins with T1D.
Implications for Precision Medicine
The findings provide a foundation for future precision medicine approaches in pediatric T1D care. The research team is building on these results through the EVERYONE study, which will explore how individual factors such as insulin sensitivity, immune response, metabolism, genetics, and social health impact treatment response.
"This is opening exciting new treatment opportunities for youth with type one diabetes," Mahmud noted. "We're giving them options that are grounded in science and designed to help them thrive throughout their lives."
The study, published in Nature Medicine, was funded by Breakthrough T1D (formerly Juvenile Diabetes Research Foundation) and the Canadian Institutes of Health Research Strategies for Patient Oriented Research program. The research aligns with Precision Child Health initiatives aimed at individualizing care for pediatric patients and families.
