Patient-Specific Considerations
New antidiabetic agents were approved for the U.S. market. They are metformin, acarbose and glimepiride. Precautions associated with their use in the patient with renal insufficiency will now be described.
Metformin (Glucophage): The biguanide hypoglycemic agent metformin (Glucophage) is approved for use in the treatment of diabetes mellitus. Metformin is indicated for use as an adjunct to diet and/or a sulfonylurea agent when either of these treatment regimens does not control hyperglycemia. The mechanism of action for metformin differs from the sulfonylureas. Metformin decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and use and by decreasing hepatic glucose production. The primary concern with metformin is the development of lactic acidosis, especially in patients with renal insufficiency.
Metformin is a congener of phenformin, also a biguanide hypoglycemic agent, which was pulled off the market in the U.S. in 1977 due to concerns with phenformin causing lactic acidosis. Metformin has also been associated with causing lactic acidosis; however, the rate of metformin-associated lactic acidosis is one-tenth that of phenformin (one in 4,000 vs. one in 40,000 – 80,000). Cases of metformin-induced lactic acidosis have occurred primarily in patients with renal insufficiency and increased age.
The biguanides can induce lactic acidosis through an increase in cellular lactate production and a decrease in the hepatic metabolism of lactate. Diabetic patients are particularly at high risk for metformin-induced lactic acidosis due to their predisposition to renal dysfunction and impaired clearance of the drug, as well as their abnormal lactate metabolism. Due to the high risk of lactic acidosis in patients with renal dysfunction, metformin is contraindicated in patients with serum creatinine levels >1.5 mg/dL for males and >1.4 mg/dL for females.
The signs and symptoms of biguanide-induced lactic acidosis are nonspecific and include (in decreasing order of frequency) vomiting, somnolence, nausea, epigastric pain, anorexia, hyperpnea, lethargy, diarrhea and thirst. The hallmark of biguanide-associated lactic acidosis is severe lactic acidosis without evidence of hypoperfusion or hypoxia. The treatment of biguanide-induced lactic acidosis is support of the circulation and removal of the drug from the body.
Acarbose (Precose): Acarbose is a complex oligosaccharide that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. In patients with renal impairment, plasma concentrations of acarbose have been shown to be proportionally increased relative to the degree of renal dysfunction. Long-term clinical trials in diabetic patients with significant renal dysfunction (serum creatinine >2.0 mg/dL) have not been conducted. Therefore, treatment of these patients with acarbose is not recommended.
Glimepiride (Amaryl): Glimepiride is a new sulfonylurea blood glucose-lowering agent. Patients with renal impairment may be more sensitive to the glucose-lowering effect of glimepiride. Thus, in patients who have renal dysfunction, a starting dose of 1 mg once daily followed by appropriate dose titration is recommended. Pharmacist’s Involvement
With the provision of pharmaceutical care, the pharmacist should be closely involved with the diabetic patient in renal failure and can offer the patient assistance in several health-care areas, including the management of his/her diabetes. The pharmacist can educate the patient about diabetes, its complications and the importance of controlling blood glucose levels through proper diet, exercise and use of medications. The proper use of a blood glucose machine to monitor home blood glucose levels can also be taught by the pharmacist, as well as frequently measuring and monitoring the patient’s blood glucose. Since hypertension can worsen renal function, the pharmacist should also periodically monitor the patient’s blood pressure and teach the patient how to measure his or her blood pressure at home. In monitoring blood glucose and blood pressure, the pharmacist also needs to assess the patient’s diet, activity level and health status.
In addition, the pharmacist should evaluate the patient’s drug therapy — assessing not only the medication’s efficacy, but also the medication’s effect on blood glucose, blood pressure, electrolytes, lipids and renal function. The patient’s optimal drug therapy, lifestyle, blood glucose, blood pressure and renal function must be monitored to prevent further complications.Summary
Renal failure seriously impacts the quality of life and management of the diabetic patient. There are numerous patient considerations that the pharmacist must evaluate. Additionally, an understanding of the effect renal failure has on insulin greatly assists the pharmacist who is providing pharmaceutical care to the diabetic patient with renal insufficiency.