Combining insulin treatment with the investigational drug dapagliflozin may improve health outcomes for adolescents with type 1 diabetes, according to a clinical trial led by endocrinologist Farid Mahmud of The Hospital for Sick Children (SickKids) and the University of Toronto's Temerty Faculty of Medicine.
For the study, Mahmud and colleagues assessed 98 patients between the ages of 12 to 18 who were given either dapagliflozin or placebo, in addition to their standard insulin therapy. Combination therapy was shown to improve blood sugar control, boost kidney function and reduce weight gain.
The findings, published in Nature Medicine , could help guide precision care for young T1D patients at risk of chronic kidney disease.
"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 Mahmud, an associate scientist and staff endocrinologist at SickKids and an associate professor in the department of paediatrics and Institute of Medical Science at Temerty. "This could inform a new early intervention strategy for the growing population of teenagers with type one diabetes."
T1D is a chronic autoimmune condition that causes the pancreas to stop producing insulin, a hormone that controls blood sugar levels.
While most patients are diagnosed as adults, TD1 often starts in childhood and early adolescence. The condition requires insulin therapy throughout a person's life, which can lead to side effects such as weight gain and chronic kidney disease.
In the SickKids trial, participants who received dapagliflozin alongside insulin had fewer of these side effects and better overall health outcomes.
While previous research has shown similar results in adults, Mahmud's team focused on designing a clinical trial specifically for teenagers, a group often underrepresented in clinical trials. Hormonal changes, psychological development and the shared responsibility between teens and their parents for managing treatment protocols can make trial participation more complex for this age group.
To address these challenges, the research team worked closely with patient partner Lynne McArthur, whose involvement in research began when one of her twin sons was diagnosed with T1D following a visit to the SickKids emergency department at just 18 months old. A few years later, his twin was also diagnosed.
That experience led McArthur to become more involved in research efforts to improve diagnosis and treatment options for families like hers. "Deciding to participate in a clinical trial is an important decision, but my goal has always been disease prevention. I knew that our participation could help build a future where children don't get T1D," says McArthur.
Now that her sons are older, McArthur continues to be involved as a patient advisor, reviewing recruitment materials, providing feedback on trial design and helping ensure that research stays connected to the lived experience of T1D patients and their families.
"Participating in research, whether in a trial or as an advisor, is hugely rewarding. With my experience as trial participant, I can see how the plans on paper would impact the real lives of people living with diabetes," explains McArthur.
The trial provides a valuable foundation for future research into precision medicine for children and adolescents with T1D. One of those opportunities is the Empowering Diverse Youth with Diabetes Through Precision Medicine (EVERYONE) study, which builds on this approach by focusing on how individual factors influence treatment response.
Aligned with SickKids's Precision Child Health movement, which aims to individualize care for patients and families, the EVERYONE study will explore how a youth's unique characteristics such as their insulin sensitivity, immune response, metabolism, genetics and social health impact how they respond to insulin treatment.
By understanding these differences between patients, the team hopes to one day inform tailored treatments to optimize outcomes for youth with T1D.
"This is opening exciting new treatment opportunities for youth with type one diabetes," says Mahmud, who is a member of the Banting & Best Diabetes Centre. "We're giving them options that are grounded in science and designed to help them thrive throughout their lives."
This study was funded by Breakthrough T1D (formerly known as Juvenile Diabetes Research Foundation, JDRF) and Canadian Institutes of Health Research Strategies for Patient-Oriented Research.
