This article is more than 5 years old. Information may no longer be current.
Diabetes medications in renal insufficiency
Click Here to Manage Email Alerts
Diabetes is the leading cause of end-stage renal disease, and clinicians are often faced with treating diabetes in patients with varying degrees of renal insufficiency. This column will briefly review the role of various diabetes medications in patients with renal insufficiency.
Sulfonylureas are classified as first- or second-generation agents. First-generation agents are rarely used in the United States and thus will not be discussed here. Glyburide undergoes metabolism to three compounds with reduced activity. About 50% of this drug is excreted in the urine. The clearance of this agent does not appear to correlate with renal function. The metabolites can accumulate in patients with renal impairment and increase risk for hypoglycemia. It has been estimated that patients with renal insufficiency who use glyburide have a fourfold increased risk for hypoglycemia. One study did not find a significant increase in hypoglycemia with low doses of glyburide in patients with ESRD compared with normal subjects. However, glyburide should not be used in patients with renal insufficiency; or it should be used cautiously.
|
|
Glipizide is metabolized in the liver to inactive metabolites. About 60% of the dose is recovered in urine. Its clearance and half-life are unaffected by renal insufficiency. There are no data indicating that risk for hypoglycemia is significantly increased because the metabolites are inactive. Thus, it is the preferred sulfonylurea in this setting. Some suggest using the regular release form as opposed to the extended release form.
Glimepiride is metabolized to an agent with less activity that undergoes renal elimination. Prolonged hypoglycemia has been reported with this agent in patients with renal impairment because the concentrations of the metabolites may increase. It may be used cautiously in patients with renal insufficiency, but is not the preferred agent in this setting.
Metformin is associated with lactic acidosis, although it is extremely rare and typically seen in patients with multiple comorbidities, including chronic kidney disease. Metformin is excreted unchanged in the urine and can accumulate in patients with glomerular filtration rates of less than 60 mL per minute and is therefore not recommended in these patients.
Thiazolidinediones are primarily hepatically metabolized into low to moderately active compounds. They may be used in patients with renal insufficiency without dose adjustment.
The meglitinides have short half lives and relatively low rates of hypoglycemia. Repaglinide is hepatically metabolized to inactive metabolites and thus can safely be used in patients with renal insufficiency. Nateglinide is primarily metabolized in the liver to moderately active metabolites, but about 15% is excreted unchanged in the urine. Thus, in patients with advanced kidney disease, the drug may accumulate and increase risk for hypoglycemia.
Exenatide is primarily renally cleared, although dose adjustment is not required for patients with a creatinine clearance of more than 30 mg/mL per minute. In patients with creatinine clearance of less than 30 mg/mL per minute, exenatide is not recommended due to significantly impaired clearance. Both sitagliptin and saxagliptin are excreted unchanged in the urine, and doses should be reduced in patients with creatinine clearance of less than 50 mg/mL per minute.
Pramlintide (Symlin, Amylin) is metabolized renally to active metabolites, but no dose adjustments are needed for creatinine clearance of more than 20 mg/mL per minute. There are no data for creatinine clearance of less than 20 mg/mL per minute.
Insulin can safely be used in patients with renal insufficiency, although the dose may need to be adjusted down because clearance may be reduced. Furthermore, patients with CKD often require less insulin to control their diabetes. The insulin analogues are generally preferred over regular and NPH insulin in the setting of CKD because they are less likely to cause hypoglycemia.
Achieving good diabetes control is important in patients with renal insufficiency to reduce overall death rates and progression of renal disease. Fortunately, numerous medication options remain for most of this population.
James R. Taylor, PharmD, CDE, is a clinical associate professor in the department of pharmacy practice at the University of Florida in Gainesville.
For more information:
- Brier ME. Am J Kidney Dis. 1997;29:907-911.
- Charpentier G. Diabetes Metab. 2000;26:73-85.
- Harrower AD. Clin Pharmacokinet. 1996;31:111-119.
- Lubowsky ND. Am J Kidney Dis. 2007;50:865-879.
- Rosenstock J. Drugs Aging. 2001;18:31-44.
- Snyder RW. Semin Dial. 2004;17:365-370.