Once-weekly insulin GZR4 versus once-daily insulin degludec in Chinese people with type 2 diabetes: A multicenter,...

Insulin GZR4 (GZR4) is a once-weekly insulin currently under development. This phase 2 trial assessed the efficacy and safety of once-weekly (QW) GZR4 versus once-daily (QD) insulin degludec (IDeg) in Chinese people with type 2 diabetes (T2D).

This 16-week, randomized, open-label, multicenter, treat-to-target phase 2 trial consisted of 2 cohorts: Cohort A enrolled insulin-naïve people; Cohort B enrolled people previously treated with basal insulin. Participants were randomly assigned (1:1) to receive GZR4 or IDeg. The primary outcome was the change in HbA1c from baseline to week 16.

Between August 22, and September 22, 2023, 179 participants were enrolled and allocated to Cohort A (n = 83) and Cohort B (n = 96). The estimated mean change in HbA1c from baseline to week 16 was -1.50 percentage points in the GZR4 group vs -1.48 percentage points in the IDeg group in Cohort A (estimated treatment difference [ETD] of -0.02 percentage points [95% CI -0.34 to 0.30], p = 0.902), -1.26 percentage points in the GZR4 group vs -0.87 percentage points in the IDeg group in Cohort B (ETD -0.38 percentage points [95% CI -0.66 to -0.11], p = 0.007). At week 16, GZR4 and IDeg group showed a similar proportion of participants achieving HbA1c targets. The treatment-emergent adverse events did not differ between two groups. The incidence of hypoglycemia (mostly level 1) was slightly higher in participants receiving GZR4 than IDeg, particularly in Cohort B. No severe hypoglycemia (level 3) was reported.

In this phase 2 trial, once-weekly GZR4 demonstrated effective glycemic control over 16 weeks in both insulin-naïve patients and those previously treated with basal insulin. The incidence of hypoglycemia was slightly higher with GZR4, particularly in the basal insulin-treated group, though no severe hypoglycemic events were reported. These findings warrant further investigation in larger phase 3 trials, which will utilize an adjusted, more precise molar-dose potency of GZR4 to fully characterize its benefit-risk profile.