Elimination and Degradation of Glucagon-like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide in Patients with End-Stage Renal Disease

Abstract

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