Diabetes, obesity & metabolism · 2026
Characterisation of steady-state pharmacokinetics and glucodynamics of once-weekly insulin efsitora alfa in individuals with type 2 diabetes.
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Leohr Jennifer, Klein Oliver, Heise Tim, Zijlstra Eric, Bue-Valleskey Juliana M, Suriyapperuma Subha, Jarrett Ryan, James Douglas, Case Micheal, Waters David, Pratt Edward, Linnebjerg Helle
Аннотация
AIMS: To evaluate the steady-state pharmacokinetics (PK) and glucodynamic effects of insulin efsitora alfa (efsitora) over a weekly interval in adults with type 2 diabetes (T2D).
MATERIALS AND METHODS: This open-label, multiple dose, euglycaemic clamp study was conducted in 56 insulin naïve adults with T2D (mean [±SD] age, 61.9 ± 5.98 years; HbA1c, 7.1 ± 0.64%; BMI, 31.7 ± 3.20 kg/m2). Following a dose-finding lead-in period with once-daily degludec, eligible participants received a one-time loading dose of 12 U/kg efsitora followed by 9 weekly doses of 4 U/kg. Three 24-h clamps were conducted on Days 1, 4, and 7 after the last efsitora dose. Model-based interpolation was used to derive the glucodynamic profile over the weekly dosing interval at steady-state.
RESULTS: Model-predicted pharmacokinetic steady-state was achieved between the 4th and 6th weekly dose of efsitora when using a one-time loading dose. At steady-state, the PK profile over the week had a low peak-to-trough ratio of 1.16, with a half-life of 19 days. The model-predicted glucose infusion rate profile, over the weekly dosing interval, demonstrated a stable glucose-lowering effect of efsitora. The maximum glucose infusion rate occurred between Days 4 and 5. Efsitora showed an even distribution of the glucose-lowering effect within a weekly dosing interval, with a peak-to-trough ratio of 1.07. Efsitora was safe and well tolerated.
CONCLUSIONS: Efsitora demonstrated a flat, prolonged PK profile, providing a consistent level of insulin exposure at steady-state and resulting in a stable glucose-lowering response across the weekly dosing interval.
MATERIALS AND METHODS: This open-label, multiple dose, euglycaemic clamp study was conducted in 56 insulin naïve adults with T2D (mean [±SD] age, 61.9 ± 5.98 years; HbA1c, 7.1 ± 0.64%; BMI, 31.7 ± 3.20 kg/m2). Following a dose-finding lead-in period with once-daily degludec, eligible participants received a one-time loading dose of 12 U/kg efsitora followed by 9 weekly doses of 4 U/kg. Three 24-h clamps were conducted on Days 1, 4, and 7 after the last efsitora dose. Model-based interpolation was used to derive the glucodynamic profile over the weekly dosing interval at steady-state.
RESULTS: Model-predicted pharmacokinetic steady-state was achieved between the 4th and 6th weekly dose of efsitora when using a one-time loading dose. At steady-state, the PK profile over the week had a low peak-to-trough ratio of 1.16, with a half-life of 19 days. The model-predicted glucose infusion rate profile, over the weekly dosing interval, demonstrated a stable glucose-lowering effect of efsitora. The maximum glucose infusion rate occurred between Days 4 and 5. Efsitora showed an even distribution of the glucose-lowering effect within a weekly dosing interval, with a peak-to-trough ratio of 1.07. Efsitora was safe and well tolerated.
CONCLUSIONS: Efsitora demonstrated a flat, prolonged PK profile, providing a consistent level of insulin exposure at steady-state and resulting in a stable glucose-lowering response across the weekly dosing interval.