The Smart MDI System in People With Type 1 Diabetes and High HBA1C: A Randomized Controlled Trial Demonstrating That Response to Alerts Drives Outcomes

Aims The aim was to assess the efficacy and safety of the smart multiple daily injections (MDI) system versus MDI plus continuous glucose monitor (CGM) in people with Type 1 diabetes and HbA1c ≥ 8%. Material and Methods After a 3‐week run‐in, 143 participants were randomized to Smart MDI or MDI + CGM. The primary endpoint was between‐group difference (Δ) in time‐in‐range (TIR) at 6 months, adjusted for baseline glycaemia and assessed for non‐inferiority (margin 7.5%). Secondary endpoints included HbA1c (non‐inferiority margin 0.4%) and superiority analyses for TIR and HbA1c. Smart MDI alerts prompt insulin bolus actions (in contrast to traditional CGM alerts), and post hoc analyses were performed to evaluate ‘alert‐responsiveness’ on glycaemia. Alert‐responsiveness findings were validated in a real‐world cohort of 5507 users. Safety endpoints were assessed. Results At 6 months, Δ TIR between groups was 0.19 percentage points (95% confidence interval: −4.9 to 5.3), thus meeting non‐inferiority; HbA1c also met non‐inferiority (Δ: −0.13 percentage points, −0.46 to 0.19) but neither showed superiority. Post hoc analyses showed higher responders to alerts (those responding more than the median response rate of 28.3%, n = 31) had greater TIR gains than lower responders ( n = 28) (+8.12 percentage points; p = 0.04) and HbA1c reduction (−0.6 percentage points; p = 0.02). TIR benefits in higher responders were confirmed in the real‐world cohort. One episode of diabetic ketoacidosis occurred (run‐in) and one severe hypoglycaemic event occurred (control arm). Conclusions Smart MDI is safe and non‐inferior, achieving non‐inferiority to MDI + CGM regarding TIR and HbA1c. Responding to as few as 28% of alerts resulted in glycaemic improvements.