Glucose-lowering drugs in patients with chronic kidney disease: a narrative review on pharmacokinetic properties

Abstract

The achievement of a good glycaemic control is one of the cornerstones for preventing and delaying progression of microvascular and macrovascular complications in patients with both diabetes and chronic kidney disease (CKD). As for other drugs, the presence of an impaired renal function may significantly affect pharmacokinetics of the majority of glucose-lowering agents, thus exposing diabetic CKD patients to a higher risk of side effects, mainly hypoglycaemic episodes. As a consequence, a reduction in dosing and/or frequency of administration is necessary to keep a satisfactory efficacy/safety profile. In this review, we aim to summarize the pharmacology of the most widely used glucose-lowering agents, discuss whether and how it is altered by a reduced renal function, and the recommendations that can be made for their use in patients with different degrees of CKD.

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

“…In general, first-generation sulfonylureas should be avoided in patients with CKD stages 3 or 4 or those who are undergoing dialysis, in whom gliclazide and glipizide are suitable without extensive dose adjustment [71][72][73] . Glimepiride is an option for patients with CKD but not receiving dialysis, on the proviso of low-dose initiation and careful titration 71,73 .…”

The efficacy and safety of dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus patients with severe renal impairment: a meta-analysis

“…Similarly, the SAVOR-TIMI 53 trail, 12 which uses a prespecified renal safety composite endpoint, showed that saxagliptin did not increase the risk of impaired kidney function. However, in spite of this, dose adjustment is recommended for all medications except linagliptin 13 (because 80% of linagliptin is eliminated unchanged in feces 14 ). In general, DPP-4 inhibitors are fairly tolerable and safe.…”

Hypoglycaemic Effect of Glibenclamide: A Critical Study on the Basis of Creatinine and Lipid Peroxidation Status of Streptozotocin-induced Diabetic Rat

“…Diabetes mellitus is a leading cause of kidney damage and develops chronic kidney disease later in life [8] . This is because of haemodynamic changes and further free radical generation in hyperglycaemia [9,10] .…”

“…But, the metabolism is incomplete due to lack of tolerance of the organs to different drug doses. Conversely, nonmetabolized content of the hypoglycaemic agent, which accumulates in the above organs worsened their normal functions [8] .…”

“…Sometimes antidiabetic medicines cause rare side effects including renal failure, hepatic dysfunction or tissue ischemia [50] . A study reported that impaired renal function is one of the consequences of glucose lowering agents [8] . It indicates that oral antidiabetic in experimental diabetes.…”