AUGMENTed Real-World Data Enhances Comparative Efficacy Between Once-Weekly Insulin Icodec with Dosing Guide App Versus Once-Daily Insulin Glargine U300 in Insulin-Naive Type 2 Diabetes

ONWARDS 5 evaluated the effectiveness and safety of insulin icodec (icodec) titrated with a dosing guide app (icodec with app) versus once-daily insulin analogs in insulin-naive adults with type 2 diabetes. The insulin glargine U300 (glargine U300) stratum was too small to enable a robust post hoc efficacy comparison. Augmentation methodology was applied to increase the glargine U300 group size using real-world data (RWD), to facilitate efficacy comparisons of icodec with app versus glargine U300, and to demonstrate the potential of the augmentation methodology to strengthen underpowered treatment comparisons (AUGMENT study). ONWARDS 5 data were augmented with RWD collected from the US Ambulatory Electronic Medical Records database. Randomized and augmented comparisons (propensity-score-matched) between icodec with app and glargine U300 were weighted to provide a fully augmented estimate of the primary outcome (change in glycated hemoglobin [HbA1c] after 52 weeks). Data were adjusted for trial effects. Sensitivity analyses were conducted. The nonaugmented randomized estimated treatment difference (ETD; 95% CI) between icodec with app and glargine U300 (trial stratum) for change in HbA1c was − 0.21 (− 0.70 to 0.28) percentage points. After adjusting for trial effects, the overall fully augmented ETD (95% CI) was − 0.33 (− 0.68 to 0.01) percentage points numerically in favor of icodec with app, although not statistically significant. Sensitivity analyses supported the findings. Using augmented data, the precision of the change in HbA1c estimate was increased compared with the trial stratum analysis alone. These findings help to validate the principle of utilizing augmentation to strengthen trial outcomes. The ONWARDS 5 trial is registered with ClinicalTrials.gov (NCT04760626).