Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Expert Opin Drug Metab Toxicol. 2013 May;9(5):529-50. doi: 10.1517/17425255.2013.777428. Epub 2013 Mar 6.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Publication types

  • Review

MeSH terms

  • Creatinine / urine
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Glomerular Filtration Rate
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemia / drug therapy
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / therapeutic use*
  • Metformin / pharmacokinetics
  • Metformin / therapeutic use
  • Randomized Controlled Trials as Topic
  • Receptors, Glucagon / agonists
  • Receptors, Glucagon / genetics
  • Receptors, Glucagon / metabolism
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / metabolism
  • Sodium-Glucose Transporter 2 / genetics
  • Sodium-Glucose Transporter 2 / metabolism
  • Sulfonylurea Compounds / pharmacokinetics
  • Sulfonylurea Compounds / therapeutic use

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Receptors, Glucagon
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sulfonylurea Compounds
  • Metformin
  • Creatinine