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

Abstract

SUMMARYIntroduction : 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. 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.

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

“…Thus, caution is required, especially in patients with severe HI. In contrast to patients with CLD, in patients with chronic kidney disease, several studies have been published, which combine not only PK analysis after a single administration but also clinical efficacy/safety data after chronic administration up to 1 year in T2DM patients [22] . Such long-term clinical studies are not available in diabetic patients with CLD.…”

“…Therefore, renal function should be carefully monitored in all patients with cirrhosis and selection of antidiabetic pharmacotherapy should also take into account the possibility of associated renal impairment in such patients [22] . This is of major importance because the dosage of DPP-4 inhibitors (except linagliptin) should be adjusted to the glomerular filtration rate and there are restrictions regarding the use of GLP-1 receptor agonists in presence of moderate to severe kidney insufficiency [14,22] .…”

“…This is of major importance because the dosage of DPP-4 inhibitors (except linagliptin) should be adjusted to the glomerular filtration rate and there are restrictions regarding the use of GLP-1 receptor agonists in presence of moderate to severe kidney insufficiency [14,22] .…”

Drug–Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus

“…Caution is thus recommended in the interpretation of the available data, which could not be automatically extrapolated to patients with T2DM, especially when comorbidities are present such as chronic kidney disease (CKD) [19,25] or hepatic impairment [19] .…”

SGLT2 versus DPP4 inhibitors for type 2 diabetes

“…In general, the subjective tolerance profile was slightly better with DPP-4 inhibitors than with SGLT-2 inhibitors. No comparative study concerned patients with renal impairment 10 Most of these trials were rather short-term (12-24 weeks) so that it is difficult to conclude on the long-term efficacy of each compound. Durability of the glucose-lowering effect is a crucial issue because T2DM is an evolving disease and progressive metabolic deterioration is commonly observed with all available glucose-lowering agents.…”