Postprandial ultra-fast insulin versus mealtime fast-acting insulin in adults with cystic fibrosis-related diabetes: A randomized multicentre crossover trial

Aims Postprandial administration of ultra-fast-acting insulin (PP-UFI) may offer greater flexibility for individuals with cystic fibrosis–related diabetes (CFRD). This study evaluated whether PP-UFI provides glycaemic control comparable to standard mealtime fast-acting insulin (MT-FI). Methods Adults with CFRD were enrolled in an open-label, multicentre, randomized phase IV crossover trial with a two-sequence, four-period design. Participants received MT-FI or PP-UFI using connected insulin pens for 3-month periods. The primary endpoint was time in range (TIR: 70–180 mg/dL). Mixed-effects models accounted for repeated measures and treatment sequence. Results Thirty-eight participants were enrolled (mean age: 33 ± 11 years; 56% receiving CFTR modulators), and 34 were included in the intention-to-treat analysis. Baseline TIR was 74% [68–83], time below range (<70 mg/dL) was 4.1% [1.9–6.7], and ppFEV1 was 71 ± 25%. The estimated difference between MT-FI and PP-UFI was + 1.1 percentage points (95% CI: −1.1 to + 3.3; p = 0.316), with no statistically significant difference observed. Formal equivalence was not demonstrated. Other CGM metrics, HbA1c, and insulin doses were comparable between treatments. Conclusion These findings support the potential of postprandial ultra-fast-acting insulin as a flexible treatment option for adults with CFRD.