Long-term efficacy and safety of Control-IQ technology in younger children with type 1 diabetes in Italy (2020-2023): a longitudinal multicentre real-world study

Background: Automated insulin delivery (AID) systems have demonstrated significant improvements in glycemic control in children and adults with type 1 diabetes, but long-term real-world data in preschool-aged children remain limited, particularly in Europe, where Control-IQ is not approved for children under 6 years. This study aimed to evaluate the long-term effectiveness and safety of the t:slim X2 insulin pump with Control-IQ technology in children aged 0.5-5 years compared with those aged 6-10 years in a real-world multicenter Italian cohort. Methods: In this longitudinal, observational study conducted from 2020 to 2023, data were collected from 32 Italian centers on children <11 years diagnosed with type 1 diabetes for at least six months and using the t:slim X2 with Control-IQ technology (CIQ). Participants were grouped into 0.5-5 years or 6-10 years at CIQ initiation. Primary endpoints were the percentage of time spent in range (TIR, 70-180 mg/dL) and in tight range (TITR, 70-140 mg/dL) in the two age groups, evaluated according to children's demographic, socioeconomic, and clinical characteristics using mixed-effects models for repeated measures. Findings: We evaluated 253 children with 18-month follow-up, 131 into the 0.5-5-year group and 122 in the 6-10-year group. In the 0.5-5-year group, TIR and TITR increased significantly from baseline to 6 months and were then maintained through 18 months. In the 6-10-year group, similar improvements were observed, with no statistically significant differences between age groups in the TIR or TITR trajectories. In the adjusted mixed-effects models, TIR increased from baseline to 6 months by 5.45% (95% CI 3.78-7.11) and TITR increased by 5.56% (95% CI 3.60-7.51), with stabilization thereafter. Children of parents with a high level of education had a significantly greater mean TIR. A longer interval between T1D diagnosis and CIQ initiation was associated with a lower mean TITR (-1.21%, 95% CI -2.32 to -0.10). During observation, there were no episodes of severe hypoglycemia in younger children and only one episode in a 6-10-year-old. One episode of DKA occurred after the start of CIQ in a younger child. Interpretation: CIQ was associated with sustained improvements in glycemic outcomes, especially within the first six months. Adverse events were rare. These findings support potential supervised off-label use in young children. Funding: No specific funds were received for this study.