Better Glycemic Control with Once-Weekly Insulin Icodec vs. Once-Daily Insulin Degludec in Insulin-Naive Type 2 Diabetes (ONWARDS 3)

Efficacy and safety of once-weekly insulin icodec (icodec) vs once-daily insulin degludec (degludec) in insulin-naïve adults with T2D were examined in ONWARDS 3 (NCT04795531), a 26-week, randomized, double blind, double dummy, treat-to-target, phase 3a trial. Participants (n=588) were randomized 1:1 to icodec or degludec. Key outcomes are shown in the table. The primary endpoint was A1C change from baseline (BL) to week 26. Estimated mean A1C change was greater with icodec (−1.57%; BL: 8.55%) vs degludec (−1.36%; BL: 8.48%); estimated treatment difference −0.21%-points (95% CI −0.34, −0.08), confirming non-inferiority (p<0.0001) and superiority (p=0.0016). Level 2 or 3 hypoglycemia rates were numerically but not statistically significantly higher with icodec vs degludec in the on-treatment period. Odds of achieving A1C <7% without level 2 or 3 hypoglycemia were statistically significantly higher with icodec vs degludec. There were no significant differences in weekly insulin dose from week 24 to 26 or body weight change from BL to week 26 between arms. No unexpected safety findings were observed. Overall, once-weekly icodec demonstrated superior A1C reduction vs once-daily degludec with low level 2 or 3 hypoglycemia rates in both arms. Icodec may facilitate insulin treatment acceptance and adherence by reducing basal insulin injections from ≥365 to 52 per year. Disclosure I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp & Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim. M.Asong: Employee; Novo Nordisk. C.Desouza: Advisory Panel; Novo Nordisk A/S, Bayer Inc., Consultant; Asahi Kasei Corporation, Research Support; Eli Lilly and Company. P.Gourdy: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Sanofi, Bayer Inc., Merck Sharp & Dohme Corp., Novartis, Intercept Pharmaceuticals, Inc., Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Sanofi, Abbott, AstraZeneca, Boehringer-Ingelheim. S.Kar: None. A.G.Vianna: Advisory Panel; AstraZeneca, Board Member; Abbott Diabetes, Novo Nordisk, Medtronic, Research Support; Novo Nordisk, Anji Pharmaceuticals, Lilly, Speaker's Bureau; AstraZeneca, Novo Nordisk, Medtronic. T.Vilsbøll: Consultant; AstraZeneca, Boehringer Ingelheim Inc., Gilead Sciences, Inc., Eli Lilly and Company, Mundipharma, Merck & Co., Inc., Novo Nordisk A/S, Sanofi, Sun Pharmaceutical Industries Ltd., Bristol-Myers Squibb Company. S.M.Vinther: Employee; Novo Nordisk. Y.Mu: Speaker's Bureau; Abbott Diabetes, Boehringer Ingelheim Inc., Novo Nordisk (China), Sanifit. Funding Novo Nordisk A/S