Adjunct-to-insulin therapy using SGLT2 inhibitors in youth with type 1 diabetes: a randomized controlled trial.

Sodium glucose co-transporter 2 inhibitors (SGLT2i) reduce the risk of chronic kidney disease (CKD) progression in type 2 diabetes, but their effects in type 1 diabetes (T1D) are not completely understood. ATTEMPT (Adolescent Type 1 Diabetes Treatment with SGLT2i for Hyperglycemia and Hyperfiltration Trial) is a 22-week, double-blind, randomized, placebo-controlled trial to assess dapagliflozin, as an adjunct to insulin, in youth with T1D. Ninety-eight participants (12-21 years of age, 53% female) were randomly assigned to dapagliflozin 5 mg or placebo alongside ketone monitoring and diabetic ketoacidosis (DKA) risk mitigation education. The primary outcome was change in measured glomerular filtration rate (mGFR) using iohexol clearance. Dapagliflozin reduced mGFR by 8.8 ml min 1.73 m when compared to placebo (95% confidence interval (CI): -12.7 to -4.8; P < 0.0001), and participants with higher baseline mGFR experienced greater attenuation with dapagliflozin (r: -0.58; P < 0.0001). HbA1c decreased by 0.47% (95% CI: -0.66 to -0.28), and time in range (glucose levels 70-180 mg dl, 4-10 mmol L) increased by 9.0% (95% CI: 3.8-14.3). Body weight decreased by 2.8 kg (95% CI: -3.7 to -2.0) with dapagliflozin. No differences were observed with respect to total daily insulin dose (U kg). Adverse events were similar between groups, with one mild DKA case in the dapagliflozin group. 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. ClinicalTrials.gov: NCT04333823 .