A phase 1b, randomized, open-label study of once-weekly insulin GZR4 in patients with type 2 diabetes mellitus

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.