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ATTEMPT trial shows kidney, glycemic benefits for SGLT2 inhibitor in adolescents with type 1 diabetes


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The sodium-glucose cotransporter protein-2 (SGLT2) inhibitor dapagliflozin appears to be safe and effective for improving kidney function and glycemic management in adolescents with type 1 diabetes taking insulin. The first randomized controlled trial of an SGLT2 inhibitor in adolescents with type 1 diabetes showed an 8.44-point reduction in measured glomerular filtration rate and an A1C decline of 0.48 percent compared to placebo.

Farid H. Mahmud, MD
Farid H. Mahmud, MD

“Adjunctive therapy with an SGLT2 inhibitor did improve kidney health and lower blood sugars,” said Farid H. Mahmud, MD, Staff Physician and Associate Scientist, Translational Medicine, Hospital for Sick Children, and Associate Professor of Medicine, University of Toronto, Canada. “These results are interesting, but longer term studies are needed to assess if dapagliflozin will slow the rate of decline in kidney function in type 1 diabetes.”

Dr. Mahmud presented the results of the ATTEMPT trial during the symposium Use of SGLT2i in Youth with Type 1 Diabetes—Results from ATTEMPT (The Adolescent Type 1 Diabetes Treatment with SGLT2i for hyperglycEMia & hyPerfilTration Trial) on Monday, June 24, at the 84th Scientific Sessions.

Jennifer L. Sherr, MD, PhD, Professor of Pediatrics and Pediatric Endocrinology at Yale University School of Medicine, had a less muted assessment of the trial.

Jennifer L. Sherr, MD, PhD
Jennifer L. Sherr, MD, PhD

“ATTEMPT was a call to action,” she said. “The time is now to integrate this adjunctive therapy into clinical practice.”

Children and adolescents with type 1 diabetes are among the highest risk groups for early morbidity and mortality, said Petter Bjornstad, MD, Professor of Pathology and of Medicine, University of Washington (UW) Medicine, and Director of the UW Medicine Diabetes Institute. Young people with type 1 diabetes have a shorter life expectancy than the general population by 8­–13 years.

Cardiovascular disease (CVD) is the primary cause of premature death in type 1 diabetes, and diabetes-related kidney disease commonly leads to CVD and death, he noted.

“We need to mitigate premature mortality and narrow the mortality gap for our youth,” Dr. Bjornstad said. “We need to mitigate early diabetic kidney injury in young people.”

Petter Bjornstad, MD
Petter Bjornstad, MD

SGLT2 inhibitors have already been approved to slow progression of kidney disease and decrease the risk of kidney failure and cardiovascular death in type 2 diabetes, he added. Adult studies suggest similar protective benefits in type 1 diabetes, but there have been no previous randomized controlled trials of any SGLT2 inhibitor in adolescents or children with type 1 diabetes.

ATTEMPT randomized 98 patients with type 1 diabetes to dapagliflozin 5 mg once daily or placebo for 22 weeks. All participants had type 1 diabetes and were on insulin. Patients were 12–17 years old, about half female and three-quarters white, with a mean body mass index (BMI) of 25 and a mean A1C of 7.7 percent. About 70 percent used insulin pumps.

Samantha Anthony, PhD, MSW, RSW
Samantha Anthony, PhD, MSW, RSW

The trial included a patient-centered diabetes-related ketoacidosis (DKA) risk-mitigation strategy that included routine ketone self-monitoring and a protocol to mitigate potential DKA events. There was a single case of mild DKA in the dapagliflozin arm with other adverse events similar across both arms.

ATTEMPT also focused on patient-reported outcome measures to assess the personal, familial, and social impact of SGLT2 treatment. A series of 24 semi-structured interviews captured participants’ personal experiences and perspectives.

“We found that adolescents didn’t mind being in the trial,” said Samantha Anthony, PhD, MSW, RSW, Health Clinician Scientist, Transplant and Regenerative Medicine Centre, Hospital for Sick Children, and Associate Professor of Social Work, University of Toronto. “They told us that taking an oral drug did not add to the burden of their current type 1 diabetes daily management.”

Participants also reported that adherence was easy—with reminders—and the patient education built into ATTEMPT helped them avoid feeling stressed when they missed a dose.