%0 Journal Article
%A McKie, Elizabeth A
%A Reid, Juliet L
%A Mistry, Prafull C
%A DeWall, Stephen L
%A Abberley, Lee
%A Ambery, Philip D
%A Gil-Extremera, Blas
%T A Study to Investigate the Efficacy and Safety of an Anti-Interleukin-18 Monoclonal Antibody in the Treatment of Type 2 Diabetes Mellitus.
%D 2016
%U http://hdl.handle.net/10668/2454
%X 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.
%K Anticuerpos monoclonales humanizados
%K Glucemia
%K Diabetes Mellitus tipo II
%K Farmacoterapia combinada
%K Humanos
%K Hipoglucemiantes
%K Interleucina-18
%K Metformina
%K Obesidad
%K Método con una ocultación
%K Resultado del tratamiento
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