(DCP051) IMPROVED A1C AND TIME IN RANGE WITH ONCE-WEEKLY INSULIN ICODEC VERSUS INSULIN GLARGINE U100 IN INSULIN-NAÏVE TYPE 2 DIABETES: ONWARDS 1

Background: The long-term efficacy and safety of once-weekly insulin icodec (icodec) vs once-daily insulin glargine U100 (glargine U100), both with non-insulin glucose-lowering agents, including SGLT2i and GLP-1 RA, were assessed in ONWARDS 1.

METHODS AND RESULTS: ONWARDS 1 was a randomized, open label, treat-to-target, multinational, phase 3a trial (52-week + 26-week extension) in insulin-naïve adults with type 2 diabetes. Participants (n=984) were randomized 1:1 to icodec or glargine U100. The prespecified primary analysis at week 52 showed A1C reduction from a baseline (BL) of 8.5% to 6.9% with icodec vs 8.4% to 7.1% with glargine U100 (estimated treatment difference [ETD]: −0.19%-points [95% CI: −0.36, −0.03]), confirming non-inferiority (p < 0.0001) and superiority (p=0.0210) of icodec vs glargine U100. The percentage of time spent in range (TIR 3.9–10.0 mmol/L [70–180 mg/dL]) at week 48–52 significantly improved to 72% (icodec) vs 67% glargine U100), confirming icodec superiority; ETD 4.27%-points ([1.92; 6.62], p=0.0004). Time spent >10.0 mmol/L (>180 mg/dL) at week 48–52 was significantly lower with icodec vs glargine U100 (27% vs 32%, ETD: −4.58%-points [−6.99, −2.17], p=0.0002), while time spent < 3.0 mmol/L ( < 54 mg/dL) was similar (0.3% vs 0.2%, estimated treatment ratio: 1.27 [0.94, 1.71], p=0.1134). Mean change in fasting plasma glucose was similar between arms (ETD: –0.01
[–0.27, 0.24], p=0.9200). There were no significant differences in mean weekly insulin dose (week 50–52), or in body weight change from BL (table). Rates of level 2 or 3 hypoglycemia (BL to week 52) were low in both groups, with numerically higher rates with icodec. A higher proportion of participants achieved A1C < 7% without level 2 or 3 hypoglycemia with icodec vs glargine U100 (52.6% vs 42.6%, p=0.0028).

Conclusion: ONWARDS 1 demonstrated the totality of glycemic evidence of once-weekly icodec vs glargine U100, with significantly improved A1C, more time spent in range and more participants achieving A1C < 7.0% without level 2 or 3 hypoglycemia in inadequately controlled insulin-naïve type 2 diabetes, with low hypoglycemia rates in both arms.