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.