A novel ultra-long-acting insulin formulation (insulin icodec) requiring only once-weekly subcutaneous injection achieved HbA1c control statistically non-inferior to daily insulin degludec in patients with type 1 diabetes, with a significantly lower rate of clinically significant hypoglycemia and dramatically improved patient-reported treatment satisfaction scores in the ONWARDS 6 Phase 3 trial.
The Burden of Daily Insulin Injections
Type 1 diabetes management currently requires at minimum one to two injections of long-acting basal insulin per day (many patients inject daily or twice daily), in addition to multiple rapid-acting mealtime doses — totaling an average of five to seven injections daily for those on multiple daily injection (MDI) regimens. For the 1.6 million Americans with type 1 diabetes, this represents an enormous physical and psychological treatment burden sustained over a lifetime.
Non-adherence to basal insulin — driven by injection fatigue, pain, scheduling disruption, and stigma — is among the most common reasons for suboptimal glycemic control and preventable complications including retinopathy, nephropathy, and neuropathy.
Insulin Icodec: Pharmacology
Icodec achieves its ultra-long duration through a modified fatty acid chain that enables strong, reversible albumin binding, creating an endogenous depot from which insulin is slowly released. Its half-life of approximately 196 hours — over eight days — results in a remarkably flat pharmacokinetic profile with minimal peak-to-trough variation, theoretically reducing hypoglycemia risk from timing errors.
ONWARDS 6 Results
The trial enrolled 582 adults with type 1 diabetes on MDI therapy. After 26 weeks, mean HbA1c was 7.62% in the icodec group vs 7.60% in the degludec group — meeting the non-inferiority margin of 0.3%. Time-in-range (CGM 70-180 mg/dL) was 64.1% vs 64.9% — also non-inferior.
The rate of clinically significant hypoglycemia (<54 mg/dL) was 19.4 events per 100 patient-years with icodec vs 27.9 with degludec — a 30% relative reduction (p=0.002). Patient-reported outcomes on the Diabetes Treatment Satisfaction Questionnaire showed a mean improvement of 6.8 points with icodec vs 2.4 with degludec (scale 0-36).
Practical Considerations
The transition to once-weekly dosing requires patient education about the “loading” phenomenon during initiation — increased hypoglycemia risk in the first two weeks as steady-state is established — and careful sick-day management given that a missed dose cannot be corrected same-day. Specialized dose-adjustment algorithms are being developed and incorporated into diabetes management apps.
Regulatory Status
The FDA approved insulin icodec for type 2 diabetes in 2025. Supplemental approval for type 1 diabetes based on ONWARDS 6 data is under active review, with a decision expected in Q4 2026.
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