Effect of hemodialysis on plasma glucose profile and plasma level of liraglutide in patients with type 2 diabetes mellitus and end-stage renal disease: a pilot study

PLoS One. 2014 Dec 19;9(12):e113468. doi: 10.1371/journal.pone.0113468. eCollection 2014.

Abstract

The effect of hemodialysis on the plasma glucose profile and liraglutide level after liraglutide injection was investigated in patients with diabetes and end-stage renal disease (ESRD). Either 0.6 mg or 0.9 mg liraglutide was subcutaneously administered daily to 10 Japanese type 2 diabetic patients with ESRD. Hemodialysis was conducted on days 1 and 3. Plasma liraglutide and glucose concentrations were measured by enzyme-linked immunosorbent assay and a continuous glucose monitoring system, respectively. The safety profile of liraglutide was also assessed. Hemodialysis had no effect on the pharmacokinetic parameters of liraglutide in patients with diabetes and ESRD; the maximum plasma concentration (Cmax), tmax, area under the concentration-time curve (AUC), and CL/f were unaltered. Similarly, hemodialysis did not affect the mean or minimum glucose levels, AUC, or duration of hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) following liraglutide administration. However, significant increases in mean amplitude of glycemic excursions (MAGE) and standard deviation (SD) as markers of glucose fluctuation, and the maximum glucose level were observed during hemodialysis. No adverse events, including hypoglycemia, were observed after liraglutide injection, either off-hemodialysis (day 2) or on-hemodialysis (day 3). Liraglutide was well tolerated in patients with type 2 diabetes and ESRD undergoing hemodialysis. The present results suggested that hemodialysis did not affect the pharmacokinetic profile of liraglutide or most glycemic indices, with the exception of MAGE, SD, and the maximum glucose level. These results suggested that it may be possible to use liraglutide during hemodialysis for diabetes with ESRD, without dose adjustment. Trial Registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000010159.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / blood*
  • Hypoglycemic Agents / therapeutic use
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy*
  • Liraglutide / adverse effects
  • Liraglutide / blood*
  • Liraglutide / therapeutic use
  • Male
  • Middle Aged
  • Pilot Projects
  • Renal Dialysis / adverse effects*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Liraglutide

Associated data

  • figshare/10.6084/M9.FIGSHARE.1254643

Grants and funding

This trial was funded by Novo Nordisk A/S (Denmark). Novo Nordisk didn’t participate in the design, conduct, or reporting of this trial. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.