Once-weekly insulin icodec: pharmacology, phase 3 evidence and clinical positioning

Author

Dr. Nihit Soni, Dr. Manoj Kumar Saurabh

Abstract

 Insulin icodec is the first once-weekly basal insulin, and weekly dosing changes how basal insulin is started, switched and monitored. We review the molecular design, pharmacokinetics and pharmacodynamics of icodec, the phase 3a ONWARDS 1-6 programme in type 2 and type 1 diabetes, and regulatory milestones to September 2026. Literature was identified in PubMed using the terms insulin icodec, ONWARDS and once-weekly insulin. In type 2 diabetes, icodec was non-inferior in all five trials and statistically superior in four, with combined level 2 or 3 hypoglycemia below one event per patient-year in the basal-only trials; in the basal-bolus trial ONWARDS 4 rates were elevated in both arms (5.64 vs 5.62 events per patient-year), a regimen effect rather than a drug effect. In type 1 diabetes, ONWARDS 6 showed non-inferior HbA1c but about double the clinically significant hypoglycemia (19.9 vs 10.4 events per patient-year), and that indication is not approved in the United States. Time in range improved in ONWARDS 1 despite nearly identical fasting glucose, so fasting glucose alone under-detects benefit. Icodec suits insulin-naive or basal-only type 2 diabetes where adherence limits control, monitored with continuous glucose monitoring where available.

Keywords

Insulin, Long-Acting; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Hypoglycemia; Blood Glucose Self-Monitoring; Drug Approval

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