title: Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease.
abstract: BACKGROUND
  People with chronic kidney disease (CKD) of stages 3 - 5 (creatinine clearance < 60 ml/min) represent ≈ 25% of patients with type 2 diabetes mellitus (T2DM), but the problem is underrecognized or neglected in clinical practice. However, most oral antidiabetic agents have limitations in case of renal impairment (RI), either because they require a dose adjustment or because they are contraindicated for safety reasons.
  
  
  METHODS
  The author performed an extensive literature search to analyze the influence of RI on the pharmacokinetics (PK) of glucose-lowering agents and the potential consequences for clinical practice.
  
  
  CONCLUSIONS
  As a result of PK interferences and for safety reasons, the daily dose should be reduced according to glomerular filtration rate (GFR) or even the drug is contraindicated in presence of severe CKD. This is the case for metformin (risk of lactic acidosis) and for many sulfonylureas (risk of hypoglycemia). At present, however, the exact GFR cutoff for metformin use is controversial. New antidiabetic agents are better tolerated in case of CKD, although clinical experience remains quite limited for most of them. The dose of DPP-4 inhibitors should be reduced (except for linagliptin), whereas both the efficacy and safety of SGLT2 inhibitors are questionable in presence of CKD.
authors: University of Liège, Division of Diabetes, Nutrition and Metabolic Disorders, Division of Clinical Pharmacology, Department of Medicine, CHU Sart Tilman (B35), Liège, Belgium. andre.scheen@chu.ulg.ac.be
authors: André J
authors: AJ
authors: Scheen
mesh_terms: D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D005919:Glomerular Filtration Rate; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008687:Metformin / Q000493:pharmacokinetics / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018027:Receptors, Glucagon / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000235:genetics / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D018027:Receptors, Glucagon; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D013453:Sulfonylurea Compounds; D008687:Metformin; D003404:Creatinine