179-OR: Improved A1C and TIR with Once-Weekly Insulin Icodec vs. Insulin Glargine U100 in Insulin-Naïve T2D—ONWARDS 1

Abstract

Long-term efficacy and safety of once-weekly insulin icodec (icodec) vs insulin glargine U100 (IGlar), both with non-insulin glucose-lowering agents, including SGLT2i and GLP‑1 RA, were assessed in this randomized, open-label, treat-to-target phase 3a trial (52-week + 26-week extension) in insulin-naïve adults with T2D (NCT04460885). Participants (n=984) were randomized 1:1 to icodec or IGlar. 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 IGlar (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. Time spent in target glycemic range (TIR, from week 48-52) was significantly improved to 72% (icodec) vs 67% (IGlar), confirming superiority; ETD 4.27%-points (95% CI: 1.92; 6.62, p=0.0004). There were no significant differences in mean weekly insulin dose (week 50-52), or in body weight change from BL. Level 2 or 3 hypoglycemia rates (BL to week 52) were low in both groups, with numerically higher rates with icodec. A higher proportion achieved A1C <7% without level 2 or 3 hypoglycemia with icodec vs IGlar (52.6% vs 42.6%, p=0.0028). In totality, glycemic control (A1C, TIR, A1C <7% without hypoglycemia) was significantly improved by once-weekly icodec vs daily glargine U100 with low rates of hypoglycemia in both arms. Disclosure J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. S.C.Bain: Advisory Panel; Novo Nordisk, Sanofi, Lilly, Boehringer Ingelheim Inc., AstraZeneca. A.Gowda: Employee; Novo Nordisk A/S. H.Horio: Employee; Novo Nordisk. E.Jodar: Other Relationship; Amgen Inc., AstraZeneca, Eli Lilly and Company, FAES, Novo Nordisk, UCB, Inc., Speaker's Bureau; Merck & Co., Inc., Asofarma, ZP Pharmaceuticals. L.Lang lehrskov: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. 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. R.Trevisan: Advisory Panel; Novo Nordisk, AstraZeneca, Eli Lilly and Company, Other Relationship; Boehringer Ingelheim Inc., Sanofi. O.Mosenzon: Advisory Panel; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Bayer Inc., Employee; BOL Pharma, Research Support; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Speaker's Bureau; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme Corp., Sanofi. Funding Novo Nordisk A/S