Once-weekly insulin efsitora alfa matches daily glargine PK/PD and safety in Chinese T2DM.

The prevalence of Type 2 Diabetes Mellitus (T2DM) is notably high in China, where many patients rely on daily basal insulin regimens. However, the burden of daily injections often leads to suboptimal adherence, compromising glycemic control. Novel once-weekly (QW) basal insulin analogs, such as insulin efsitora alfa, are being developed to address this critical adherence gap and reduce treatment burden. This approach aims to simplify the therapeutic regimen while maintaining effective glycemic control and a favorable safety profile, thereby improving patient quality of life and long-term health outcomes.

This randomized, open-label, active-controlled, multiple-dose Phase 1 study enrolled 31 Chinese adults with T2DM already on stable daily basal insulin (± non-insulin antihyperglycemic medication). Patients were randomized 2:1 to receive either once-weekly insulin efsitora alfa or once-daily insulin glargine for 6 weeks. Pharmacokinetic (PK) parameters were evaluated using non-compartmental analysis. Pharmacodynamic (PD) endpoints included fasting plasma glucose, 7-point self-monitored blood glucose, HbA1c, and lipid profiles. Safety was assessed via treatment-emergent adverse events (TEAEs), hypoglycemia incidence, and immunogenicity.

In 31 enrolled patients (n=21 for efsitora; n=10 for glargine), insulin efsitora alfa exhibited a prolonged elimination half-life of approximately 15 days, with an apparent clearance of 0.0195 L/h and an apparent volume of distribution of 10.1 L. Both the efsitora and glargine groups showed comparable reductions in fasting glucose levels and maintained stable daily glucose profiles throughout the study. No apparent changes in HbA1c were observed in either group, and lipid profiles and C-peptide levels remained stable overall. Safety data indicated that TEAEs occurred in 81.0% of efsitora patients and 80.0% of glargine patients, with all events being mild or moderate in severity.

Notably, no deaths or study discontinuations due to adverse events were reported, and hypoglycemic events were predominantly asymptomatic and resolved with self-treatment. Furthermore, no treatment-emergent anti-drug antibodies were detected in any patient.