(DCP038) EFFICACY AND SAFETY OF ONCE-WEEKLY INSULIN ICODEC VERSUS ONCE-DAILY INSULIN DEGLUDEC IN TYPE 1 DIABETES: ONWARDS 6

Background: Efficacy and safety of once-weekly insulin icodec (icodec) vs once-daily insulin degludec (degludec) were assessed in adults with type 1 diabetes (T1D) in a randomized, open-label, treat-to-target phase 3a trial (26-week main phase + 26-week safety extension + 5-week follow-up).

METHODS AND RESULTS: Participants (n = 582) were randomized 1:1 to icodec (n = 290) or degludec (n = 292), both in combination with insulin aspart. The primary endpoint was change in A1C from baseline (BL) to week 26, tested for non-inferiority (0.3% margin). At week 26, from BL values of 7.59% (icodec) and 7.63% (degludec), estimated mean A1C changes were -0.47% and -0.51%, respectively, confirming non-inferiority of icodec vs degludec (estimated treatment difference [ETD]: 0.05%-points [95% CI: -0.13 to 0.23]). From week 22 to 26, percentage of time in range 3.9–10.0 mmol/L (70–180 mg/dL) and time spent >10.0 mmol/L (>180 mg/dL) were not statistically significantly different between treatments, while percentage of time spent < 3.0 mmol/L ( < 54 mg/dL) was statistically significantly higher with icodec vs degludec (p=0.0014). Overall rate of combined level 2 or 3 hypoglycemia (BL to week 26) was statistically significantly higher with icodec vs degludec (19.9 [icodec] vs 10.4 [degludec] events per patient-year of exposure; estimated rate ratio: 1.9 [95% CI: 1.5; 2.3]; p< 0.0001). The rate was also statistically significantly higher with icodec vs degludec when evaluated over 57 weeks. Estimated mean weekly basal dose was statistically significantly higher for icodec than degludec from week 24 to 26 (170 U/week [~24 U/day] vs 151 U/week [~22 U/day]; estimated treatment ratio [ETR]: 1.12 [95% CI: 1.07 to 1.18]; p< 0.0001), while estimated mean weekly bolus dose was statistically significantly lower (132 U/week [~19 U/day] vs 161 U/week [~23 U/day]; ETR: 0.82 [95% CI: 0.74 to 0.90]; p< 0.0001). Similar trends in insulin doses were reported for week 50 to 52.

Conclusion: In adults with T1D, once-weekly icodec showed non-inferiority in A1C reduction vs degludec at week 26 with significantly higher rate of combined level 2 or 3 hypoglycemia. For icodec, time spent < 3.0 mmol/L ( < 54 mg/dL) and < 3.9 mmol/L ( < 70 mg/dL) was either below or close to internationally recommended targets at both time points.