The following is a summary of the “Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study,” published in the March 2023 issue of Diabetes and Endocrinology by Frias, et al.
Reluctance and delays in starting insulin therapy are commonplace because of the difficulty of administering daily basal insulins. A fusion protein, basal insulin Fc (BIF, insulin efsitora alfa), combines a novel single-chain insulin variant with a human immunoglobulin G (IgG) Fc domain and is intended for weekly administration. Patients with type 2 diabetes who had been treated with basal insulin were analyzed for this study to determine if BIF was safe and effective for them. Type 2 diabetics were enrolled in this randomized, open-label, comparator-controlled, 32-week study at 44 sites (clinical research centers and hospitals) across the United States, Puerto Rico, and Mexico. Individuals over 18 treated with basal insulin and a maximum of three oral antidiabetic medications were considered eligible. 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).
Those who were eligible for randomization were separated into groups based on their country of origin, their pre-study HbA1c (<8.5% or ≥8.5%; <69.4 or ≥69.4 mmol/mol), whether or not they had previously taken sulfonylureas, and their pre-study body mass index (<30 or ≥30 kg/m2). An interactive web-response system was utilized for the randomization process, which led to a more fair distribution of participants across the various 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 ≤6.7 mmol/L (≤120 mg/dL; titrated every 4 weeks), and the degludec group was given a target of 5.8 mmol/L (≤100 mg/dL). Patients who were given BIF as part of a clinical trial were given a loading dose equal to 1.5-3 times their weekly dose. After the initial loading dose, the first weekly dose was given a week later. Basal insulin was adjusted based on interstitial fasting glucose readings obtained with a Dexcom G6 continuous glucose monitoring system. The shift in HbA1c from week 0 to week 32 was BIF’s primary indicator of glycemic control.
The effectiveness of BIF was measured against that of degludec (using a non-inferiority margin of 0-40%). Data from all randomized study participants who received at least one dose of study medication were included in the efficacy analysis set, and individuals were analyzed in accordance with the treatment they were given. Both the efficacy analysis set and the safety population were identical. About 399 people were enrolled 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; 202 (51%) were female, and 197 (49%) were male. The sample size for the primary outcome analysis was 379 (n=130 for BIF-A1, n=125 for BIF-A2, and n=124 for degludec). The primary outcome, the change in HbA1c from baseline to week 32, was -0.6% (SE -0.1%) for BIF-A1 and BIF-A2. Degludec managed a -0.7% (-0.1%) shift from the beginning point. The treatment difference in HbA1c was 0% (90 % CI -1.0% to 0.3%) in the pooled BIF analysis, which proved non-inferiority compared to degludec. Event rates of hypoglycemia (≤3.9 mmol/L or ≤70 mg/dL) in the BIF groups were 25% lower than in the degludec group (treatment ratio BIF-A1 vs. degludec was 0·75 [0·61–0·93], and BIF-A2 vs. degludec was 0·74 [0·58–0·94]). The majority of study participants who took BIF reported no serious side effects.
Although the BIF groups had more aggressive fasting glucose targets, they still achieved similar results compared to the degludec groups. In addition, compared to degludec, BIF was associated with fewer cases of hypoglycemia, which may have been due to the drug’s higher fasting glucose targets and lower glucose variability. These results lend credence to BIF’s potential as a once-weekly insulin treatment for people with diabetes.
Source: sciencedirect.com/science/article/abs/pii/S2213858722003886