Antidiabetic Agents in Patients with Chronic Kidney Disease and End-Stage Renal Disease on Dialysis: Metabolism and Clinical Practice

Abstract

Numerous drugs with different mechanisms of action and different pharmacologic profiles are being used with the aim of improving glycemic control in patients with type 2 diabetes. Therapeutic options for patients with type 2 diabetes and chronic kidney disease (CKD) are limited because a reduced glomerular filtration rate results in the accumulation of certain drugs and/or their metabolites. Conventional oral hypoglycemic agents, such as sulfonylurea (SU), are not suitable due to the risk of prolonged hypoglycemia; furthermore, metformin is contraindicated for moderate to advanced CKD. Therefore, in order to achieve good glycemic control, insulin injection therapy remains the mainstay of treatment in diabetic patients with moderate to advanced CKD, particularly in those receiving dialysis therapy. However, some agents have been used even in patients with CKD. Repaglinide and mitiglinide are rapid- and short-acting insulinotropic SU receptor ligands. They are rarely accompanied by hypoglycemia, and are attractive therapeutic options even in the dialysis population. In addition, alpha-glucosidase inhibitors are rarely accompanied by hypoglycemia and are administered without dose adjustments in dialysis patients. However, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines recommended that alpha-glucosidase inhibitors should be avoided in patients with advanced stage CKD and on dialysis. Furthermore, mitiglinide is not currently used in the US. Thus, recommended oral antidiabetic agents differ between countries. Moreover, dipeptidyl peptidase-4 inhibitors and incretin mimetics are new antihyperglycemic agents, which may be used more frequently in the future in patients with type 2 diabetes and CKD. Here, we describe the pharmacokinetics, metabolism, clinical efficacy, and safety of oral Antidiabetic agents for patients with CKD, including those receiving dialysis.

ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD – Summary

“…104 Metformin, acarbose and most sulphonylureas should be avoided in stage 3-4 CKD, whilst insulin and pioglitazone can be used. The DPP-4 inhibitors require dose adjustment with progressive CKD with the exception of linagliptin, which is well tolerated in these circumstances.…”

DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials

“…Therapeutic options for patients with T2DM and chronic kidney disease are limited because a reduced glomerular filtration rate (GFR) results in the accumulation of certain drugs and/or their metabolites [81]. The pharmacokinetic characteristics of five DPP-4 inhibitors have been studied in subjects with varying degrees of renal impairment (RI): mild = creatinine clearance 50-80 mL/min; moderate = 30-50 mL/min; and severe = < 30 mL/min, including patients with end-stage renal disease (ESRD) [5,82].…”

The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis

“…Therapeutic options for patients with type 2 diabetes and end-stage renal disease (ESRD) are, however, limited because the reduced glomerular filtration rate results in the accumulation of certain drugs and/ or their metabolites [1]. Conventional oral hypoglyce- Abstract.…”

“…mic agents, such as sulfonylurea (SU), are not suitable due to the risk of prolonged hypoglycemia, while metformin is contraindicated due to the risk of lactic acidosis in patients with ESRD [1,2]. Therefore, insulin injection therapy remains the mainstay of treatment in diabetic patients receiving hemodialysis (HD) therapy in order to achieve good glycemic control.…”