DPP-IV inhibitor used in renal failure:
A i.e. LinagliptinRef: HohIA, Ronsoni MF, Guedes EP, de Melo TG, Lauand F (2014), Linagliptin: DPP-4 Inhibition in the Treatment of Type 2, Diabetes Mellitus, J Diabetes Metab Disord Control 1(1): 00005, DOI: 10.15406/jdmdc,2014.01.00005Explanation:Patients with T2DM have dysfunction in incretin hormones (such as glucagon-like peptide-1 or GLP-1 and glucose-dependent insulinotropic polypeptide or GIP).By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level decrease in a glucose-dependent manner.Linagliptin is a dipeptidyl peptidase-4 inhibitor DPP IV inhibitor.Linagliptin is approved by FDA and EMA for the T2DM treatment as an anti-hyperglycemic agent that can be used as monotherapy or in combination with other medications (metformin, sulphonylurea, pioglitazone, metformin plus sulphonylurea or insulin).NOTE:Linagliptin is safe in renal failure, as it is eliminated majorly by biliary excretion and it also undergoes enterohepatic recycling.Chemical and metabolic characteristics of DPP-4 inhibitorsInhibitorChemical StructureMetabolitesRoute of EliminationLinagliptinBased on XanthineNegligibleBiliary(> 70% unchanged); <6% via kidneySaxagliptinCyanopyrrolidineMetabolized in the liver to active metabolite (via P450 3A4/5)Renal (12-29% unchanged and 21-52% as metabolite)SitagliptinBased on p-amino acidNegligibleRenal (80% unchanged)VildagliptinCyanopyrrolidineHydrolyzed to inactive metabolite (P450 enzyme-independent)Renal (22% unchanged and 55% as primary metabolite)AlogliptinPyrimidineDemethylated, acetylatedRenal
Linagliptin
Sitagliptin
Vildagliptin
Saxagliptin
Endocrinology