Improved glycemic management with once-weekly insulin icodec with a dosing guide app vs once-daily basal insulin analogs in insulin-naïve type 2 diabetes: onwards 5

Clinical inertia, missed insulin injections, and inadequate dose titration of basal insulins can lead to suboptimal glycemic management in individuals with T2D. ONWARDS 5, a 52-week, open-label, phase 3a trial with real-world elements, assessed effectiveness and safety of once-weekly icodec with a dosing guide app (icodec + app) vs once-daily (OD) basal insulin analogs (degludec, glargine U100, or glargine U300) in adults with insulin-naïve type 2 diabetes (T2D). To mimic clinical practice, ONWARDS 5 applied fewer exclusion criteria, including adults with any A1C >7%, age, and BMI. Choice of OD analog comparator and flexibility in background non-insulin glucose-lowering agents at the investigator’s discretion, and fewer stipulated site visits reflect further real-world elements in the trial. Participants (mean age, 59.3 years; mean BMI, 32.8 kg/m2) were randomized 1:1 to icodec or OD analogs. The dosing guide app aided icodec titration; OD analogs were initiated and titrated as per local label and standard clinical practice. The primary endpoint was change in A1C from baseline to week 52. Across 176 sites in 7 countries, 1,085 adults with insulin-naïve T2D were randomized. Estimated mean A1C change from BL to week 52 was greater with icodec + app (−1.68 percentage points, baseline 9.0%) vs OD analogs (−1.31 percentage points, baseline 8.9%); estimated treatment difference (ETD) was –0.38 percentage points (95% CI, –0.66 to –0.09), confirming non-inferiority (p<0.0001) and superiority (p=0.009) of icodec + app vs OD analogs. Patient-reported outcomes of change in Diabetes Treatment Satisfaction Questionnaire total treatment satisfaction score and mean Treatment Related Impact Measure for Diabetes compliance domain score were both statistically significantly higher for icodec + app vs OD analogs at week 52 (Table). Insulin was titrated to a significantly higher mean dose with icodec + app vs OD analogs at weeks 50–52. There was no significant difference in body weight change from baseline to week 52 between treatment arms. Level 2 (<3.0 mmol/L) or level 3 (severe) hypoglycemia rates were low and comparable in both arms (0.19 [icodec + app] vs 0.14 [OD analogs] events per person-year of exposure). The odds of achieving A1C <7% or A1C <7% without level 2 or level 3 hypoglycemia were higher with icodec than with OD analogs (Table). Treatment with once-weekly insulin icodec with a dosing guide app in adults with insulin-naïve T2D led to superior A1C reduction, greater insulin dose, and significant improvement in treatment satisfaction and compliance scores vs OD analogs, with low rates of hypoglycemia.