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Aims: To investigate the population pharmacokinetics and exposure-response relationship of liraglutide, a human glucagon-like peptide-1 (GLP-1) analogue, in Asian subjects with Type 2 diabetes mellitus., Methods: Data were derived from a published 16-week, randomized, double-blind, double-dummy, active-controlled, parallel-group trial of liraglutide in China, India and South Korea. The analysis utilized 2061 pharmacokinetic (PK) samples from 605 subjects exposed to liraglutide 0.6, 1.2 or 1.8 mg once daily. Demographic factors (body weight, age, gender, country) of importance for liraglutide clearance were evaluated. An exploratory exposure-response analysis was conducted to investigate effects on glycated haemoglobin (HbA1c) and body weight., Results: Estimated liraglutide exposure (area under the curve; AUC) appeared to increase proportionally with increasing liraglutide dose (0.6-1.8 mg). The covariate analysis confirmed previous findings in a global clinical trial. Body weight was a predictor of liraglutide exposure; compared to a reference subject of 67 kg, exposure was 32% lower for maximum (115 kg) and 54% higher for minimum (37 kg) observed body weights. Gender, age and country had no relevant effect on exposure. Exposure-response analysis supported the use of 1.2mg as maintenance dose with the option of individual dose escalation to 1.8 mg to optimize treatment outcomes., Conclusions: Exposure appeared to increase proportionally with increasing liraglutide dose in Asian subjects with Type 2 diabetes mellitus. The only PK relevant predictor of exposure was body weight. The exposure-response relationships for HbA1c and body weight in Asian subjects were similar to observations in global populations., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Aim: To assess and compare the efficacy and safety of liraglutide with those of glimepiride, both in combination with metformin for the treatment of type 2 diabetes in Asian population from China, South Korea and India., Methods: A 16-week, randomized, double-blind, double-dummy, four-arm, active control trial was carried out. In total, 929 subjects with type 2 diabetes with a mean (±s.d.) age of 53.3 ± 9.5 years, HbA₁(c) of 8.6 ± 1.0% and body weight of 68.1 ± 11.7 kg were randomized (liraglutide 0.6, 1.2 or 1.8 mg once daily or glimepiride 4 mg once daily all in combination with metformin: 1 : 1 : 1 : 1). One subject withdrew immediately after randomization and before exposure., Results: HbA₁(c) was significantly reduced in all groups compared with baseline. Treatment with liraglutide 1.2 and 1.8 mg was non-inferior to glimepiride (mean HbA₁(c) reduction: 1.36% points, 1.45% points and 1.39% points, respectively). No significant difference was shown in the percentage of subjects reaching American Diabetes Association HbA₁(c) target <7% or American Association of Clinical Endocrinologists target ≤6.5% between liraglutide 1.2 and 1.8 mg and glimepiride. Liraglutide was associated with a 1.8-2.4 kg mean weight reduction, compared with a 0.1 kg mean weight gain with glimepiride. Liraglutide led to a significantly greater reduction in systolic blood pressure (SBP) compared with glimepiride. Two subjects in the glimepiride group reported major hypoglycaemia while none in the liraglutide groups. Liraglutide was associated with about 10-fold lower incidence of minor hypoglycaemia than glimepiride. Gastrointestinal disorders were the most common adverse events (AEs) for liraglutide, but were transient and resulted in few withdrawals., Conclusions: In Asian subjects with type 2 diabetes, once-daily liraglutide led to improvement in glycaemic control similar to that with glimepiride but with less frequent major and minor hypoglycaemia. Liraglutide also induced a significant weight loss and reduced SBP and was generally well tolerated. The most frequently reported AE was transient nausea. The effect of liraglutide in this Asian population is comparable to the effects seen in Caucasian, African American and Hispanic populations in global liraglutide phase 3 trials., (© 2010 Blackwell Publishing Ltd.)

Rheumatoid arthritis (RA) is a chronic arthritic condition that can lead to deformities and disabilities. Although numerous studies reported the association of human leukocyte antigen (HLA)-DRB1*04 and RA, other genes, e.g. cytokines genes, may contribute towards disease susceptibility. Interleukin-18 (IL-18) is a proinflammatory cytokine postulated to play a role in the acute and chronic inflammatory phases of RA. The IL-18 protein expression seems to be regulated by two single-nucleotide polymorphisms (SNPs) located at positions -607 and -137 in the promoter region of the gene. It is postulated that specific alleles may be associated with susceptibility to the development of RA. In the present study, we described the IL-18 gene promoter region genotypes and combined genotypes (-607/-137) in 106 RA patients and 273 unrelated healthy controls to evaluate the contributions of these alleles to RA predisposition in Chinese, Malays, and Indians. The genotyping were performed using sequence-specific polymerase chain reactions. Rheumatoid factors were assayed by enzyme-linked immunosorbent assay. Biodata were obtained through chart review. The controls had significantly higher frequency of AA genotype at position -607 when compared to RA patients. No significant differences were observed in the distribution of either allelic or genotypic frequencies at position -137. There was no association between the genotypes and the presence of rheumatoid factors. This study did not find evidence of a genetic susceptibility factor but demonstrated the novel finding that the AA genotype at position -607 is associated with a protective effect against development of RA in Chinese individuals. This protection may be mediated through inhibition of cyclic (Adenosine 3', 5'-cyclic monophosphate) AMP-responsive element (CRE)-binding protein by the disruption of the CRE consensus sequence.