Reviews: Use of Insulin and Oral Hypoglycemic Medications in Patients with Diabetes Mellitus and Advanced Kidney Disease

Abstract

Diabetes mellitus is recognized as a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States. There is a vast array of medications used to treat diabetes, including insulin and the sulfonylureas, as well as newer classes of drugs such as the thiazolidinediones and biguanides. In patients with reduced glomerular filtration rate (GFR), it is necessary to decrease the dosage of some of these drugs, while others are best avoided altogether. Accumulation of either the parent compound or its metabolites can result in symptomatic hypoglycemia, or in the case of metformin, significant lactic acidosis. In this article we will review the use of insulin and the various classes of oral medications used to treat type 2 diabetes mellitus, focusing on their pharmacokinetic properties and dosing in patients with advanced kidney disease.

Management of type 2 Diabetes in patients with Chronic Kidney Disease

“…• There occurs less renal gluconeogenesis as a result of reduction in renal mass in CKD patients (4).…”

Management of Diabetes in Patients on Hemodialysis

“…Since the kidney function in minimal in ESRD and the drug is not dialyzable, it can cause hypoglycemia thus are contraindicated in this setting. As far as second generation SU like glipizide, gliclazide and glimepiride are concerned, they are metabolized in the liver but most of their active metabolites are excreted by the kidney [17]. The exception to this is glipizide that is metabolized in the liver to inactive-weakly active metabolites that are excreted by the kidney.…”

“…Biguanides are contraindicated in this setting [17]. Thizolidinediones are peroxisome proliferator-activated receptor gamma (PPAR) agonists which enhance insulin sensitivity and reduce hepatic glucose production [18].…”

“…These drugs are also accumulated in renal failure and are not recommended for use in this setting. Besides, the added disadvantage of gastrointestinal side effects has made this class loose favor [17].…”

“…Although a consensus approach is lacking but most authorities endorse using rapid acting insulin like lispro before each meal alongside close monitoring of blood glucose [17]. Use of basal insulin has been controversial and reserved for those patients whose blood sugar is not under control with short acting insulin.…”