Liraglutide Treatment Is Associated with a Low Frequency and Magnitude of Antibody Formation with No Apparent Impact on Glycemic Response or Increased Frequency of Adverse Events: Results from the Liraglutide Effect and Action in Diabetes (LEAD) trials
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Liraglutide Treatment Is Associated with a Low Frequency and Magnitude of Antibody Formation with No Apparent Impact on Glycemic Response or Increased Frequency of Adverse Events : Results from the Liraglutide Effect and Action in Diabetes (LEAD) trials. / Buse, John B; Garber, Alan; Rosenstock, Julio; Schmidt, Wolfgang E; Brett, Jason H; Videbæk, Nicoline; Holst, Jens Juul; Nauck, Michael.
I: Journal of Clinical Endocrinology and Metabolism, Bind 96, Nr. 6, 2011, s. 1695-702.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Liraglutide Treatment Is Associated with a Low Frequency and Magnitude of Antibody Formation with No Apparent Impact on Glycemic Response or Increased Frequency of Adverse Events
T2 - Results from the Liraglutide Effect and Action in Diabetes (LEAD) trials
AU - Buse, John B
AU - Garber, Alan
AU - Rosenstock, Julio
AU - Schmidt, Wolfgang E
AU - Brett, Jason H
AU - Videbæk, Nicoline
AU - Holst, Jens Juul
AU - Nauck, Michael
PY - 2011
Y1 - 2011
N2 - Context: Therapeutic proteins/peptides can produce immunogenic responses that may increase the risk of adverse events or reduce efficacy. Objective: The objectives were to measure and characterize antibody formation to liraglutide, a glucagon-like peptide-1 receptor agonist, to investigate the impact on glycemic control and safety, and to compare it with exenatide, an agent in the same class. Design: Antibody data were collected during six Liraglutide Effect and Action in Diabetes (LEAD) trials (26–104 wk duration). Setting: Samples for determination of antibody formation were collected at LEAD trial sites and analyzed at central laboratories. Participants: Antibodies were measured in LEAD trial participants with type 2 diabetes. Interventions: Interventions included once-daily liraglutide (1.2 or 1.8 mg) or twice-daily exenatide (10 µg). Main Outcome Measures: The main outcome measures included the proportion of patients positive for anti-liraglutide or anti-exenatide antibodies, a glucagon-like peptide-1 cross-reacting effect, and an in vitro liraglutide- or exenatide-neutralizing effect. Change in glycosylated hemoglobin A1c (HbA1c) by antibody status and magnitude [negative, positive (high or low level)]. Results: After 26 wk, 32 of 369 (8.7%) and 49 of 587 (8.3%) patients had low-level antibodies to liraglutide 1.2 and 1.8 mg, respectively [mean 3.3% antibody-bound radioactivity out of total radioactivity (%B/T), range 1.6–10.7%B/T], which did not attenuate glycemic efficacy (HbA1c reductions 1.1–1.3% in antibody-positive vs. 1.2% in antibody-negative patients). In LEAD-6, 113 of 185 extension patients (61%) had anti-exenatide antibodies at wk 26 (range 2.4–60.2%B/T). High levels of anti-exenatide antibodies were correlated with significantly smaller HbA1c reductions (P = 0.0022). After switching from exenatide to liraglutide, anti-exenatide antibodies did not compromise a further glycemic response to liraglutide (additional 0.4% HbA1c reduction). Conclusions: Liraglutide was less immunogenic than exenatide; the frequency and levels of anti-liraglutide antibodies were low and did not impact glycemic efficacy or safety.
AB - Context: Therapeutic proteins/peptides can produce immunogenic responses that may increase the risk of adverse events or reduce efficacy. Objective: The objectives were to measure and characterize antibody formation to liraglutide, a glucagon-like peptide-1 receptor agonist, to investigate the impact on glycemic control and safety, and to compare it with exenatide, an agent in the same class. Design: Antibody data were collected during six Liraglutide Effect and Action in Diabetes (LEAD) trials (26–104 wk duration). Setting: Samples for determination of antibody formation were collected at LEAD trial sites and analyzed at central laboratories. Participants: Antibodies were measured in LEAD trial participants with type 2 diabetes. Interventions: Interventions included once-daily liraglutide (1.2 or 1.8 mg) or twice-daily exenatide (10 µg). Main Outcome Measures: The main outcome measures included the proportion of patients positive for anti-liraglutide or anti-exenatide antibodies, a glucagon-like peptide-1 cross-reacting effect, and an in vitro liraglutide- or exenatide-neutralizing effect. Change in glycosylated hemoglobin A1c (HbA1c) by antibody status and magnitude [negative, positive (high or low level)]. Results: After 26 wk, 32 of 369 (8.7%) and 49 of 587 (8.3%) patients had low-level antibodies to liraglutide 1.2 and 1.8 mg, respectively [mean 3.3% antibody-bound radioactivity out of total radioactivity (%B/T), range 1.6–10.7%B/T], which did not attenuate glycemic efficacy (HbA1c reductions 1.1–1.3% in antibody-positive vs. 1.2% in antibody-negative patients). In LEAD-6, 113 of 185 extension patients (61%) had anti-exenatide antibodies at wk 26 (range 2.4–60.2%B/T). High levels of anti-exenatide antibodies were correlated with significantly smaller HbA1c reductions (P = 0.0022). After switching from exenatide to liraglutide, anti-exenatide antibodies did not compromise a further glycemic response to liraglutide (additional 0.4% HbA1c reduction). Conclusions: Liraglutide was less immunogenic than exenatide; the frequency and levels of anti-liraglutide antibodies were low and did not impact glycemic efficacy or safety.
KW - Antibody Formation
KW - Blood Glucose
KW - Diabetes Mellitus, Type 2
KW - Female
KW - Glucagon-Like Peptide 1
KW - Humans
KW - Male
KW - Peptides
KW - Radioimmunoassay
KW - Venoms
U2 - 10.1210/jc.2010-2822
DO - 10.1210/jc.2010-2822
M3 - Journal article
C2 - 21450987
VL - 96
SP - 1695
EP - 1702
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 6
ER -
ID: 38443348