RT Journal Article
T1 A Study to Investigate the Efficacy and Safety of an Anti-Interleukin-18 Monoclonal Antibody in the Treatment of Type 2 Diabetes Mellitus.
A1 McKie, Elizabeth A
A1 Reid, Juliet L
A1 Mistry, Prafull C
A1 DeWall, Stephen L
A1 Abberley, Lee
A1 Ambery, Philip D
A1 Gil-Extremera, Blas
K1 Anticuerpos monoclonales humanizados
K1 Glucemia
K1 Diabetes Mellitus tipo II
K1 Farmacoterapia combinada
K1 Humanos
K1 Hipoglucemiantes
K1 Interleucina-18
K1 Metformina
K1 Obesidad
K1 Método con una ocultación
K1 Resultado del tratamiento
AB OBJECTIVEEvidence suggests that chronic subclinical inflammation plays an important role in the pathogenesis of type 2 diabetes (T2DM). Circulating levels of interleukin (IL)-18 appear to be associated with a number of micro- and macrovascular comorbidities of obesity and T2DM. This study was designed to investigate whether inhibition of IL-18 had any therapeutic benefit in the treatment of T2DM. Preliminary efficacy, safety and tolerability, pharmacokinetics, and pharmacodynamics of the anti-IL-18 monoclonal antibody, GSK1070806, were assessed.RESEARCH DESIGN AND METHODSThis was a multicentre, randomized, single-blind (sponsor-unblinded), placebo-controlled, parallel-group, phase IIa trial. Obese patients of either sex, aged 18-70 years, with poorly controlled T2DM on metformin monotherapy were recruited. Patients received two doses, of placebo (n = 12), GSK1070806 0.25 mg/kg (n = 13) or GSK1070806 5 mg/kg (n = 12). The primary end-point was the change from baseline in fasting plasma glucose and weighted mean glucose area under the curve (AUC)(0-4 hours) postmixed meal test on Days 29, 57, and 85.RESULTSThirty-seven patients were randomized to one of the three treatment arms. There were no statistically significant effects of GSK1070806 doses on fasting plasma glucose levels, or weighted mean glucose AUC(0-4 hours) compared with placebo.CONCLUSIONSGSK1070806 was well tolerated, and inhibition of IL-18 did not lead to any improvements in glucose control. However, because of study limitations, smaller, potentially clinically meaningful effects of IL-18 inhibition cannot be excluded.TRIAL REGISTRATIONClinicalTrials.gov NCT01648153.
PB Public Library of Science
YR 2016
FD 2016-03-01
LK http://hdl.handle.net/10668/2454
UL http://hdl.handle.net/10668/2454
LA en
NO McKie EA, Reid JL, Mistry PC, DeWall SL, Abberley L, Ambery PD, et al. A Study to Investigate the Efficacy and Safety of an Anti-Interleukin-18 Monoclonal Antibody in the Treatment of Type 2 Diabetes Mellitus. PLoS ONE. 2016; 11(3):e0150018
NO Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 10, 2025