当前位置： SCI文献检索 > POSTGRADUATE MEDICINE期刊下所有文献 > Effect of renal impairment on the pharmacokinetics, efficacy, and safety of albiglutide.

Effect of renal impairment on the pharmacokinetics, efficacy, and safety of albiglutide.

Abstract：

BACKGROUND:Chronic kidney disease is frequently present in patients with type 2 diabetes mellitus (T2DM). New therapeutic options in this patient subpopulation are needed. OBJECTIVES:Assess the effect of renal impairment on the pharmacokinetics (PK), efficacy, and safety of albiglutide in single- and multiple-dose studies. METHODS:Pharmacokinetics, safety, and efficacy of once weekly albiglutide in patients with T2DM was assessed from a single-dose (30 mg), nonrandomized, open-label study (N = 41) including subjects with normal and varying degrees of renal impairment, including hemodialysis, and a pooled analysis of 4 phase 3, randomized, double-blind (1 open-label), active or placebo-controlled multiple-dose studies. The pooled analysis of the latter 4 studies (N = 1113) was part of the population PK analysis, which included subjects with normal and varying degrees of renal impairment (mild, moderate, severe) treated with albiglutide (30 to 50 mg) to primary end points of 26 to 52 weeks. RESULTS:Single-dose PK showed area-under-the-curve ratios (and 90% CIs) of 1.32 (0.96-1.80), 1.39 (1.03-1.89), and 0.99 (0.63-1.57) for the moderate, severe, and hemodialysis groups, respectively, relative to the normal group. Results indicate that modest increases in plasma concentration of albiglutide were observed with the severity of renal impairment. There was a trend for more glycemic lowering as the estimated glomerular filtration rate decreased. The severe group had a higher frequency of gastrointestinal (eg, diarrhea, constipation, nausea, and vomiting) and hypoglycemic (with background sulfonylurea use) events compared with patients with mild or moderate renal impairment. CONCLUSION:The PK, efficacy, and safety data indicate that albiglutide has a favorable benefit/risk ratio in patients with T2DM and varying degrees of renal impairment, and the need for a dose adjustment is not suggested. Experience in patients with more severe renal impairment is very limited, so the recommendation is to use albiglutide carefully in this population. CLINICAL TRIAL REGISTRATION:(ClinicalTrials.gov):NCT00938158, NCT00849017, NCT00838916, NCT00839527, NCT0198539.

journal_name

Postgrad Med

journal_title

Postgraduate medicine

authors

Young MA,Wald JA,Matthews JE,Yang F,Reinhardt RR

doi

10.3810/pgm.2014.05.2754

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

35-46

issue

eissn

0032-5481

issn

1941-9260

journal_volume

126

pub_type

临床试验,杂志文章

在线工具

Effect of renal impairment on the pharmacokinetics, efficacy, and safety of albiglutide.