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

André J Scheen
2013 Expert Opinion on Drug Metabolism & Toxicology  
Introduction : People with chronic kidney disease (CKD) of stages 3-5 (creatinine clearance < 60 ml/min) represent 25-30% of patients with type 2 diabetes (T2DM), but the problem is underrecognized or neglected in clinical practice. However, most oral antidiabetic agents have limitations in case of renal impairment, either because they require a dose adjustment or because they are contraindicated for safety reasons. Area covered: An extensive literature search was performed to analyze the
more » ... o analyze the influence of renal impairment on the pharmacokinetics (PK) of glucose-lowering agents and the potential consequences for clinical practice. The following pharmacological classes will be considered : biguanides (metformin), sulfonylureas, meglitinides (glinides), alpha-glucosidase inhibitors, thiazolidinediones (glitazones), dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporters 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, insulin and insulin analogues. Expert Opinion : Because of potential important PK interferences and for safety reasons, the pharmacological management of T2DM should be adjusted according to kidney function. In general, the daily dose should be reduced according to glomerular filtration rate (GFR) or even the drug is contraindicated in presence of more 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 linaglitpin) whereas both the efficacy and safety of SGLT2 inhibitors are questionable in presence of CKD.
doi:10.1517/17425255.2013.777428 pmid:23461781 fatcat:v25mgdz7d5dzlhx54mobtskt5y