Un estudio aleatorizado, de etiqueta abierta, de fase 1b de insulina GZR4 una vez por semana en pacientes con...

To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of GZR4 in patients with type 2 diabetes mellitus (T2DM).

This randomized, active-controlled, phase 1b trial was conducted in adults with T2DM on stable daily basal insulin therapy. Eligible participants were randomized in 3:1 ratio within three cohorts to receive either a fixed once-weekly dose of GZR4 or once-daily insulin degludec (IDeg) subcutaneously for six weeks. Primary endpoints were incidence of adverse events (AEs), serious adverse events (SAEs), and hypoglycemia.

The most commonly reported treatment-emergent AE across all treatment groups was hypoglycemia. No SAEs or severe hypoglycemia was observed. At steady state, the mean C_max of GZR4 was 289.0 ± 17.1 to 1,016.0 ± 262.4 ng/mL; mean AUC_{GZR4, 0-168h} ranged from 34,449.6 ± 2,055.7 to 137,064.2 ± 41,496.5 h.ng/mL. Mean change in FPG from baseline to week 6 was -1.77 ± 0.20 to -2.75 ± 0.71 mmol/L for GZR4 groups and -1.12 ± 0.36 mmol/L for IDeg group; corresponding change in HbA1c was -0.38 ± 0.64 % to -0.76 ± 0.14 % versus -0.13 ± 0.21 %.

GZR4 was safe and well tolerated in patients with diabetes in present trial with pharmacokinetic and pharmacodynamic profiles enabling once-weekly dosing.