Novel Once-Weekly Basal Insulin Fc Achieved Similar Glycemic Control With a Safety Profile Comparable to Insulin Degludec in Patients With Type 1 Diabetes

• Published in: Diabetes care Vol. 46; no. 5; pp. 1052 - 1059
• Main Authors: Kazda, Christof M, Bue-Valleskey, Juliana M, Chien, Jenny, Zhang, Qianyi, Chigutsa, Emmanuel, Landschulz, William, Wullenweber, Paula, Haupt, Axel, Dahl, Dominik
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.05.2023
• Subjects: Blood Glucose - metabolism; Blood Glucose Self-Monitoring; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - chemically induced; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 2 - chemically induced; Fasting; Fusion protein; Glucose; Glucose monitoring; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Hypoglycemia - chemically induced; Hypoglycemic Agents - adverse effects; Immunoglobulin G; Insulin; Insulin - adverse effects; Insulin Glargine; Original; Research design; Safety; Statistical analysis
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc22-2395

Basal Insulin Fc (BIF; insulin efsitora alfa; LY3209590), a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for once-weekly basal insulin administration. This phase 2 study assessed safety and efficacy of BIF versus degludec in 265 patients with type 1 diabetes (T1D) using multiple daily injections. During this randomized, parallel, open-label study, patients with T1D were randomized (1:1) to receive BIF once weekly or degludec once daily over the 26-week treatment period. Both groups were titrated to a fasting glucose level of 80-100 mg/dL. The primary end point was HbA1c change from baseline to week 26 (noninferiority margin, 0.4%). Secondary end points included percent time in range (TIR) (70-180 mg/dL), continuous glucose monitoring (CGM) fasting glucose (FG) level, and rate of hypoglycemia. After 26 weeks, patients receiving BIF had noninferior HbA1c change from baseline versus those receiving degludec, with a statistically significant treatment difference of 0.17% (90% CI 0.01, 0.32; P = 0.07) favoring the comparator. Percent TIR was similar for patients in the BIF (56.1%) and degludec (58.9%; P = 0.112) groups at week 26. FG values were significantly higher for patients receiving BIF (158.8 mg/dL) versus degludec (143.2 mg/dL; P = 0.003). Rates of CGM-derived hypoglycemia were not statistically significantly different for BIF and degludec over 24 h for level 1 (P = 0.960) or level 2 (P = 0.517) hypoglycemia during the treatment period. Occurrence of serious adverse events was similar between the BIF and degludec groups. Once-weekly BIF demonstrated noninferior glycemic control to once-daily degludec (treatment difference: 0.17% favoring degludec) and no difference in hypoglycemia or other safety findings in patients with T1D.