The following is a summary of “Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomized, phase 2 study,” published in the March 2023 issue of Diabetes and Endocrinology by Frias et al.
The daily administration of basal insulins can lead to reluctance and postponement in the commencement of insulin therapy. The Basal Insulin Fc (BIF), or insulin efsitora alfa, is a fusion protein developed for weekly administration. It comprises a unique single-chain insulin variant and a human immunoglobulin G (IgG) Fc domain. The present study investigates the safety and efficacy of BIF in individuals diagnosed with type 2 diabetes mellitus who had previously undergone basal insulin therapy. In this phase 2 study, researchers enrolled individuals diagnosed with type 2 diabetes from 44 clinical research centers and hospitals in the United States, Puerto Rico, and Mexico. The study was randomized, open-label, comparator-controlled, and lasted 32 weeks. Inclusion criteria necessitated that eligible subjects were of adult age (≥18 years) and had received treatment with basal insulin in conjunction with a maximum of three oral antidiabetic agents. The subjects were randomized in a 1:1:1 ratio to receive subcutaneous injections of either BIF (BIF-A1 or BIF-A2) or insulin degludec. The randomization process was stratified based on the participant’s country of origin, baseline HbA1c levels (<8.5% or ≥8.5%; <69.4 or ≥69.4 mmol/mol), usage of sulfonylureas (yes or no), and baseline BMI (<30 or ≥30 kg/m2). The randomization scheme utilized an interactive web-based response system, which guaranteed equipoise among the treatment cohorts.
Distinct fasting glucose objectives were chosen for the BIF-A1 (≤7·8 mmol/L or ≤140 mg/dL; adjusted every 2 weeks), BIF-A2 (≤6·7 mmol/L or ≤120 mg/dL; adjusted every 4 weeks), and degludec (≤5·6 mmol/L or ≤100 mg/dL) cohorts. Individuals subject to random allocation were administered a loading dose once, which varied from 1.5 to 3 times their weekly calculated dose in the case of BIF. The initial weekly administration was carried out seven days following the loading dosage. The basal insulin was titrated using interstitial fasting glucose measurements obtained from the Dexcom G6 continuous glucose monitoring system. The principal indicator of glycemic regulation was the alteration in HbA1c levels from the initial assessment to the 32nd week for BIF. In addition, BIF was subjected to a comparative analysis with degludec, with a non-inferiority margin of 0.40%. The set for efficacy analysis comprised information from all randomized participants and administered at least one dose of the study medication. The analysis was conducted based on the treatment assigned to each participant. The safety cohort was identical to the efficacy evaluation group. During the period spanning from November 15th, 2018, to February 18th, 2020, a total of 399 individuals were recruited and subjected to randomization, with 135 being assigned to BIF-A1, 132 to BIF-A2, and 132 to degludec.
The study population comprised 202 females (51%) and 197 males (49%). 379 subjects were evaluated for the primary outcome, with 130 subjects receiving BIF-A1, 125 subjects receiving BIF-A2, and 124 subjects receiving degludec. The primary outcome, the mean change in HbA1c from baseline to week 32, was -0.6% (standard error 0.1%) for both BIF-A1 and BIF-A2. The administration of Degludec resulted in a reduction of 0.7% (0.1%) from the baseline. The analysis of pooled basal insulin formulations (BIF) demonstrated non-inferiority in comparison to degludec regarding the treatment difference in glycated hemoglobin (HbA1c) levels (0.1% [90% CI -0.1 to 0.3]). The incidence of hypoglycemia (having a blood glucose level of ≤3·9 mmol/L or ≤70 mg/dL) in the BIF groups was 25% lower than in the degludec group. The treatment ratio for BIF-A1 vs degludec was 0·75 [0·61–0·93], and for BIF-A2 vs degludec was 0·74 [0·58–0·94]. The BIF medication was well-tolerated, and no significant differences in treatment-emergent adverse events were observed among the groups. The weekly basal insulin formulation (BIF) demonstrated comparable effectiveness to degludec, despite the BIF group having higher fasting glucose targets. The lower incidence of hypoglycemia observed in BIF as compared to degludec may be attributed to the employment of higher fasting glucose targets and reduced glucose variability. The aforementioned observations substantiate the ongoing advancement of BIF as a weekly insulin therapy for individuals with diabetes.