Abstract
INTRODUCTION: This analysis aimed to assess the safety and tolerability of insulin efsitora alfa (efsitora, basal insulin Fc, LY3209590) and characterize the pharmacokinetic and pharmacodynamic profiles of efsitora in Japanese patients with type 2 diabetes. METHODS: The single-dose escalation study assessed once-weekly efsitora administration in three patient cohorts: 5 mg for cohort 1; 10 mg for cohort 2 or placebo under double-blind conditions; and 20 mg for cohort 3 under open-label conditions. In the 6-week, multiple-dose study, patients started or continued using insulin degludec during the lead-in period, followed by randomization to efsitora (individualized fixed weekly dose) or insulin degludec (individualized fixed daily dose). Pharmacokinetics, pharmacodynamics, and safety were examined. RESULTS: The mean age was 58.3 and 58.4 years, and mean body mass index was 25.6 and 26.8 kg/m(2) in the single-dose escalation (n = 31) and multiple-dose studies (n = 28), respectively. The pharmacokinetic profile showed a prolonged half-life of 15 to 16 days, with a low peak-to-trough ratio of 1.13 after the last dose with little fluctuation. All doses of efsitora (5, 10, and 20 mg) decreased mean fasting glucose levels from baseline to day 15 (single-dose study), with no notable changes observed after switching from insulin degludec (multiple-dose study). All treatment-emergent adverse events were mild and unrelated to the study drug. No severe hypoglycemic events were reported. CONCLUSIONS: Efsitora was well tolerated, and the pharmacokinetic and pharmacodynamic profiles were consistent with findings in prior global studies, supporting the participation of Japanese patients in phase 3 studies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03603704; NCT04276428.