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 need for daily basal insulins is a significant barrier to initiating insulin therapy. As a fusion protein, basal insulin Fc (BIF, insulin efsitora alfa) combines a unique single-chain insulin variation with a human immunoglobulin G (IgG) Fc domain and is intended for weekly delivery. Here, the researchers investigated the feasibility and performance of BIF in basal insulin-naive individuals with type 2 diabetes. Researchers recruited those suffering from type 2 diabetes in the United States, Puerto Rico, and Mexico for a 32-week, randomized, open-label, controlled trial at 44 sites (clinical research centers and hospitals). Subjects were adults (over 18) on combination therapy of basal insulin and up to 3 oral antidiabetic medications to qualify. Subcutaneous BIF (BIF treatment group 1 [BIF-A1] or 2 [BIF-A2]) or insulin degludec was administered to study participants in a randomized, double-blind, placebo-controlled trial (1:1:1). There were 4 different strata for the randomization process: nation, pre-treatment HbA1c (<8.5% vs. ≥8.5%; <69.4 vs. ≥69.4 mmol/mol), sulfonylurea use (yes or no), and body mass index (<30 vs. ≥30 kg/m2). An online, user-responsive randomization method was used to create fair treatment groups. 

The BIF-A1 group was given a target of ≤7.8 mmol/L (≤140 mg/dL; titrated every 2 weeks), the BIF-A2 group was given a target of ≤6.8 mmol/L (≤120 mg/dL; titrated every 4 weeks), and the degludec group was given a target of ≤5.6 mmol/L (≤100 mg/dL). Those given BIF as part of a clinical trial were given a loading dose 1.5-3 times their weekly dosage. A week following the loading dose, the first weekly dose was given. To fine-tune the basal insulin, we employed the Dexcom G6 continuous glucose monitoring system’s glucose readings in the interstitial fluid. Change in HbA1c from baseline to week 32 was used as the major indicator of glycaemic control for BIF. Also, degludec was compared to BIF (with a non-inferiority margin of 0-40%). Data from all randomized study participants who took at least one dosage of the study medicine were combined to form the efficacy analysis set, and individuals were analyzed based on the therapy they were given. Those who participated in the efficacy and safety analyses were the same people. About 399 people, including 202 (51% female) and 197 (49% male), were registered and randomly assigned to receive either BIF-A1 (n=135), BIF-A2 (n=132), or degludec (n=132) between November 15, 2018, and February 18, 2020. 

To determine the primary outcome, 379 samples were analyzed (n=130 for BIF-A1, n=125 for BIF-A2, and n=124 for degludec). The primary endpoint, the change in HbA1c from baseline to week 32, was found to be -0.6% (SE -0.1%) for both BIF-A1 and BIF-A2. Degludec managed a -0.7% (-0.1%) deviation from baseline. The treatment difference in HbA1c was 0.1% [90% CI -0.1 to 0.3] in the pooled BIF study, which was not inferior to degludec. Compared to the degludec group, the BIF groups had 25% lower rates of hypoglycemia (≤3·9 mmol/L or ≤70 mg/dL) events (hypoglycemia events per patient per year) 0·75 [0·61–0·93]; and BIF-A2 vs. degludec was 0·74 [0·58–0·94]). In addition, it was found that BIF was generally well tolerated, with no significant differences in the incidence of treatment-emergent adverse events between the 2 groups. Despite higher fasting, glucose targets in the BIF groups, weekly BIF achieved equivalent efficacy compared to degludec. The lower hypoglycemia rates for BIF relative to degludec may have resulted from higher fasting glucose objectives and lower glucose variability. These results lend credence to the idea that BIF has promise as a once-weekly insulin treatment for diabetics.

Source: sciencedirect.com/science/article/abs/pii/S2213858722003886