ATTEMPT: Dapagliflozin Improves Renal Function, Glycemic Control in Children with Type 1 Diabetes

Farid Mahmud, MD

Credit: SickKids Research Institute

Dapagliflozin may be a safe and effective option to improve kidney function and glycemic management in youth and adolescents with type 1 diabetes, according to findings from a recent study.¹

The study, ATTEMPT, is the first trial designed to evaluate the effectiveness of sodium-glucose cotransporter-2 (SGLT2) inhibitors to optimize diabetes control and prevent early subclinical kidney complications in an at-risk pediatric population with type 1 diabetes. Findings were presented during a late-breaking session at the 84th American Diabetes Association (ADA) Scientific Sessions.¹

“This study paves the way for us to evaluate treatments that can reduce kidney disease progression for those with type 1 diabetes,” lead investigator Farid Mahmud, MD, a physician in the division of endocrinology in the department of pediatrics and associate professor at the University of Toronto, said in a press release.¹ “These findings also give us meaningful insights as we look how we optimize diabetes management in youth and young adults during a challenging period associated with kidney disease progression and above-target A1c.”

According to the American Diabetes Association, in 2021, 38.4 million people in the US, or 11.6% of the population, had diabetes. Of these individuals, an estimated 2 million have type 1 diabetes, including about 304,000 children and adolescents. Diabetes is the leading cause of kidney disease, underscoring the importance of considering renal health in patients with diabetes.²

Dapagliflozin earned US Food and Drug Administration (FDA) approval for adults with type 2 diabetes in 2014. In 2021, dapagliflozin became the first SGLT2 inhibitor to receive FDA approval for the treatment of chronic kidney disease in patients with and without type 2 diabetes. Specifically, it was approved for reducing the risk of kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with CKD at risk of disease progression.^3,4

A double-blind, randomized, placebo-controlled trial, ATTEMPT evaluated the impact of dapagliflozin in combination with insulin therapy in adolescents with type 1 diabetes. Over a 16-week monitoring period, investigators assessed detailed renal mechanistic evaluations with direct measurement of glomerular filtration rate (GFR), glycemic control (HbA1c), and safety outcomes in 98 participants with type 1 diabetes, providing essential information for establishing a framework for young adolescents to evaluate key physiologic, mechanistic, and metabolic outcomes when using SGLT2i alongside insulin in type 1 diabetes.¹

Findings showed the safety of low-dose dapagliflozin for improving kidney function and glycemic management. Treatment with low-dose dapagliflozin attenuated direct measures of GFR and was associated with a significant decline in HbA1c of 0.48% (P = .001). Of note, no significant differences were observed in the proportion of participants who experienced adverse events, elevated ketone levels, hypoglycemia, and genitourinary tract infections in the dapagliflozin versus placebo groups.¹

Investigators called attention to a single case of mild diabetic ketoacidosis (DKA) in the dapagliflozin group. While rates of DKA were low, they noted a greater number of elevated blood ketone events ≥0.6mmol/L were seen in the dapagliflozin group (n = 106) compared with the placebo group (n = 62; P <.001), emphasizing the patient-centered DKA Risk Mitigation Education strategy operationalized during the study.¹

Investigators pointed out the trial was designed with protocols to successfully mitigate the risk of DKA, something they emphasized the importance of considering before SGLT2 inhibitors can be widely used in clinical practice. They also noted the ATTEMPT trial paves the way for researchers to produce longer studies to help better understand the additional benefits of adjunctive therapy in type 1 diabetes.¹

References:

1. ^{American Diabetes Association. Common Type 2 Diabetes Drug Shown to Safely Reduce the Progression of Kidney Disease in Adolescents with Type 1 Diabetes. June 24, 2024. Accessed June 24, 2024.}
2. ^{American Diabetes Assosciation. Statistics About Diabetes. Accessed June 24, 2024. https://diabetes.org/about-diabetes/statistics/about-diabetes}
3. ^{Campbell, P. Dapagliflozin (Farxiga) Receives Historic FDA Approval for Chronic Kidney Disease. HCPLive. April 30, 2021. Accessed June 24, 2024. https://www.hcplive.com/view/dapagliflozin-farxiga-receives-historic-fda-approval-for-chronic-kidney-disease}
4. ^{Drugs.com. Farxiga FDA Approval History. June 17, 2024. Accessed June 24, 2024. https://www.drugs.com/history/farxiga.html}