808-P: Pharmacokinetic Properties of Once-Weekly Insulin Icodec in Individuals with Renal Impairment vs. Normal Renal Function

Abstract

Insulin icodec is a once-weekly basal insulin in development. This trial investigated if renal impairment affects the pharmacokinetics (PK) of icodec. In an open-label, parallel-group trial, 58 individuals (39 males; mean±SD age 50±13 yrs, BMI 26.5±3.1 kg/m2) were allocated to five groups according to renal function based on measured glomerular filtration rate (GFR): normal renal function (NRF; ≥90 mL/min; N=12), mild (60 to <90 mL/min; N=12), moderate (30 to <60 mL/min; N=12), severe (<30 mL/min; N=12) renal impairment and end‑stage renal disease (N=10). A single s.c. icodec dose (1.5 U/kg) was administered and blood was sampled for PK until 840 h (35 days) post-dose. A minor increase was observed in total exposure (AUC0-840h,SD) with decreasing GFR, but the estimated effect of GFR on AUC0-840h,SD did not differ statistically significantly from zero (-0.069; 95% CI [-0.150;0.013]; p=0.099). Pairwise group comparisons showed numerically slightly higher AUC0-840h,SD and Cmax,SS for renal impairment vs NRF (Figure). AUC0-840h,SD was statistically significantly higher for moderate renal impairment vs NRF. In conclusion, icodec exposure trended to be slightly higher for renal impairment vs NRF. The clinical relevance is however limited as icodec should be dosed according to individual need. Thus, no specific dose adjustment of icodec is required in individuals with renal impairment. Disclosure H.Haahr: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. N.R.Kristensen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. J.H.Larsen: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. F.H.Wagner: None. S.Ignatenko: None. Funding Novo Nordisk