Context: The impact 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. Design and study subjects: Twelve non-diabetic patients treated with chronic hemodialysis and 12 control subjects were examined in a double-blinded, randomized, matched, observational study. Setting: Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Intervention: Over 4 separate study days, synthetic human GIP or GLP-1 was infused with or without concurrent inhibition of DPP-4 using sitagliptin or placebo. Main outcome measures: 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 < 0.001), whereas fasting levels of GLP-1 and GIP metabolites did not differ between groups (P > 0.738). MCRs of intact GLP-1 and GIP, and the GLP-1 metabolite were reduced in dialysis patients on the placebo day (P < 0.009), while T1/2 of intact and metabolite forms of GLP-1 and GIP were comparable between groups (P > 0.121). Conclusions: Unexpectedly, degradation and elimination of the intact and metabolite forms of GLP-1 and GIP appeared preserved, although reduced, in patients with dialysis-dependent kidney failure.
Journal of Clinical Endocrinology and Metabolism, 2014, Vol 99, Issue 7, p. 2457-66