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

Introduction: People with chronic kidney disease (CKD) of stages 3 - 5 (creatinine clearance < 60 ml/min) represent approximate to 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.