Elimination and degradation of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with end-stage renal disease

J Clin Endocrinol Metab. 2014 Jul;99(7):2457-66. doi: 10.1210/jc.2013-3809. Epub 2014 Apr 8.


Context: The affect of the kidneys in elimination and degradation of intact incretin hormones and their truncated metabolites is unclear.

Objective: To evaluate elimination and degradation of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in patients with dialysis-dependent kidney failure.

Setting and design: Twelve non-diabetic patients treated with chronic hemodialysis and 12 control subjects were examined in a double-blind, randomized, matched observational study at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Over 4 separate study days, synthetic human GIP or GLP-1 was infused with or without concurrent inhibition of dipeptidyl peptidase 4 using sitagliptin or placebo. Plasma concentrations of glucose, insulin, glucagon, and intact and total forms of GLP-1 or GIP were measured repeatedly. Plasma half-life (T1/2), metabolic clearance rate (MCR), area under curve, and volume of distribution for intact and metabolite levels of GLP-1 and GIP were calculated.

Results: Fasting concentrations of intact GLP-1 and GIP were increased in dialysis patients (P < .001) whereas fasting levels of GLP-1 and GIP metabolites did not differ between groups (P > .738). MCRs of intact GLP-1 and GIP, and the GLP-1 metabolite were reduced in dialysis patients on the placebo day (P < .009), and T1/2 of intact and metabolite forms of GLP-1 and GIP were comparable between groups (P > .121).

Conclusions: Unexpectedly, degradation and elimination of the intact and metabolite forms of GLP-1 and GIP seemed preserved, although reduced, in patients with dialysis-dependent kidney failure.

Trial registration: ClinicalTrials.gov NCT01391884.

Publication types

  • Observational Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Denmark
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Fasting / blood
  • Fasting / urine
  • Female
  • Gastric Inhibitory Polypeptide / administration & dosage
  • Gastric Inhibitory Polypeptide / pharmacokinetics*
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / pharmacokinetics*
  • Humans
  • Insulin / blood
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacokinetics*
  • Proteolysis
  • Pyrazines / administration & dosage
  • Renal Dialysis / adverse effects
  • Sitagliptin Phosphate
  • Triazoles / administration & dosage


  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Insulin
  • Peptide Fragments
  • Pyrazines
  • Triazoles
  • gastric inhibitory polypeptide (1-42)
  • glucagon-like peptide 1 (7-36)amide
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Dipeptidyl Peptidase 4
  • Sitagliptin Phosphate

Associated data

  • ClinicalTrials.gov/NCT01391884