Efficacy and Safety of Different Commercially Available Hybrid Closed-Loop Systems in People with Type 1 Diabetes: An up to Date Systematic Review with Meta-Analysis and Network Meta-Analysis

Introduction: In type 1 diabetes, hybrid closed-loop (HCL) systems have proven effective in improving glucose control without increasing time below range (TBR). We aimed to compare the performance of different HCL systems through a meta-analysis and network meta-analysis of randomized controlled trials (RCTs). Methods: We searched MEDLINE, EMBASE, CENTRAL, PubMed, and conference proceedings up to April 18, 2025, and ultimately included RCTs involving children, adolescents, and adults with type 1 diabetes, with baseline HbA1c 7.0%–8.5%, comparing HCL systems with other forms of insulin therapy, and reporting time in range (TIR). Results: A total of 32 RCTs were analyzed. Among the 22 RCTs with a mean participant age ≥ 18 years, Omnipod 5, MiniMed 780G, and iLet BP improved TIR by approximately 20% over subcutaneous insulin therapy (SIT) without continuous glucose monitoring (high certainty); of the three, only MiniMed 780G achieved a mean end-of-study TIR > 70%. In the 10 RCTs with participants < 18 years, Control IQ showed the greatest improvement in TIR, although none of the systems reached a mean TIR > 70%. All HCL systems reduced TBR compared with SIT in studies with participants ≥ 18 years but showed similar effects to SIT in younger populations. The risk of severe hypoglycemia and diabetic ketoacidosis was low and similar to other treatment strategies. Conclusions: In RCTs involving individuals with type 1 diabetes, HCL systems demonstrate a hierarchy of efficacy compared with SIT, which also appear to be influenced by the mean age of participants.