title: Insulin degludec does not increase antibody formation versus insulin glargine: an evaluation of phase IIIa trials.
abstract: We examined insulin antibody formation in patients with type 1 (T1D) or type 2 diabetes (T2D) treated with once-daily insulin degludec (IDeg) or insulin glargine (IGlar) to evaluate the impact of antibody formation on efficacy and safety. Insulin antibodies were measured using subtraction radioimmunoassays in six phase IIIa clinical trials using IDeg (n = 2250) and IGlar (n = 1184). Spearman's correlation coefficient was used to evaluate associations between cross-reacting antibodies and change from baseline glycated haemoglobin (HbA1c) and insulin dose. IDeg- and IGlar-specific antibodies remained low [<1% bound/total radioactivity (B/T)] and with low levels of antibodies cross-reacting with human insulin in patients with T1D (<20% B/T) and T2D (<6% B/T). Spearman's correlation coefficients between insulin antibody levels and change in HbA1c or insulin dose were low in both treatment groups. No clinically meaningful differences in adverse event (AE) rates were observed in patients with >10% B/T or without an absolute increase in antibodies cross-reacting with human insulin. IDeg treatment resulted in few immunogenic responses in patients with T1D and T2D; antibody formation was not associated with change in HbA1c, insulin dose or rates of AEs.
authors.affiliation: Department of Diabetes and Endocrinology, Royal Liverpool University Hospitals, Liverpool, UK.
authors.forename: J
authors.initials: J
authors.lastname: Vora
authors.affiliation: Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg, Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Seufert
authors.affiliation: Novo Nordisk A/S, Måløv, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Solberg
authors.affiliation: Novo Nordisk A/S, Bagsvaerd, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Kinduryte
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Johansen
authors.affiliation: Baylor Endocrine Center, Dallas, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Hollander
mesh_terms: D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D017326:Clinical Trials, Phase III as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology; D004334:Drug Administration Schedule; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007111:Immunity, Cellular / Q000502:physiology; D007330:Insulin Antibodies / Q000378:metabolism*; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007330:Insulin Antibodies; D049528:Insulin, Long-Acting; C571886:insulin degludec
keywords: insulin antibodies; insulin degludec; long-acting insulin; type 1 diabetes; type 2 diabetes