- Similar to meglitinides, sulfonylureas stimulate the pancreas to secrete more insulin, but the insulin secretion is not related to increasing blood sugar levels. These drugs are therefore more likely to cause low blood sugar levels or hypoglycemia. Common sulfonylureas are Micronase®(glyburide), Glucotrol®(glipizide) and Amaryl®(glimepiride).
- Glyburide use should be avoided in patients with severe kidney impairment as defined by a GFR of less than 60 mL/min (CKD stage 3 and below). Because 50 percent of the glyburide is excreted by the kidneys, the drug can build up in people with CKD, causing low blood sugar levels.
- Glipizide is the most commonly used oral medication in patients with advanced kidney disease, and no specific dosage adjustment is required for glipizide; however, the manufacturer recommends conservative initial and maintenance glipizide doses as well as careful blood glucose monitoring to avoid hypoglycemic reactions.
- In people with CKD and ESRD, glimepiride should be dosed conservatively and dose changes should be based on fasting blood glucose concentrations.
- The most common side effect is low blood sugar. All patients taking sulfonylureas should recognize the symptoms and know how to treat them because severe hypoglycemia is possible with all medications in this class.Other side effects depend on the specific medication.
- Thiazolidinedionesimprove the effectiveness of insulin by decreasing insulin resistance in muscle and fat tissues and lower the amount of glucose released by the liver. Medicines include Actos® (pioglitazone) and Avandia® (rosiglitazone).
- People with cardiovascular problems should not be prescribed Avandia®. Because many people with CKD and ESRD also have heart disease, Avandia® may not be prescribed for them.
- No specific dosage adjustments are required with Actos, and it can be used safely in conjunction with insulin.
- Thiazolidinediones have come under increased scrutiny, including some restrictions for their use by the FDA due to the severity of their side effects such as fluid retention, worsening of heart and lung disease, and liver failure.
Dipeptidyl peptidase 4 (DPP-4) inhibitors
- Examples of these medications are Januvia®(sitagliptin) and Onglyza®(saxagliptin). They lower blood sugar levels by increasing insulin secretion from the pancreas and decreasing the amount of glucose that is produced by the liver.
- After Januvia®was marketed, reports of worsening kidney function, even acute kidney failure, were described. No such events were reported for Onglyza®.
- Therefore, the use of Januvia®may require dosing adjustments for patients with a GFR of less than or equal to 50 mL/min (CKD stage 3 and below) and these patients should discuss individual dosing with their endocrinologist and nephrologist.
- Common side effects for both drugs include headache, runny or stuffy nose, sore throat, upper respiratory infection, nausea and upset stomach.
- Precose® (acarbose) and Glyset® (miglitol) slow the digestion of carbohydrates and thereby decrease the rate at which glucose is absorbed from food in the intestines. They will not cause low blood sugar unless they are taken with other oral diabetes medications or insulin.
- Experience with acarbose treatment in patients with severe renal impairment is limited; the manufacturer does not recommend the use of acarbose in this patient population.
- If acarbose treatment is warranted, it should be used cautiously in patients with severe renal impairment and people with Stage 3 and 4 CKD, or those on dialysis should consult their nephrologist before taking these medications.
- Gastrointestinal side effects are the most common and consist of diarrhea, gas, bloating, nausea and stomach pain.
Biguanides and Combination Therapy
- The main action of these medications is decreasing the amount of glucose that is produced by the liver. In addition, actions of medications in this class include stimulating the pancreas to produce more insulin, decreasing the body’s resistance to insulin, and increasing the amount of glucose absorbed by muscle cells. Generic names are metformin (Glucophage®)and a combination of repaglinide and metformin (Prandimet®).
- It is important to note that even though metformin may be the first-line treatment for most patients, metformin is contraindicated in patients with severe renal impairment as defined by a glomerular filtration rate (GFR) of less than 60 mL/min (stage 3 CKD and below). In hemodialysis patients, metformin use is an absolute contraindication —when a drug should not be used —because it increases risk of lactic acidosis (an increase in acid in the tissues and blood), which can lead to death.
- The most common side effects of metformin are temporary nausea, loss of appetite, diarrhea, increased abdominal gas and a metallic taste.
- Meglitinides stimulate the pancreas to secrete more insulin in response to increasing blood sugar levels. Two examples of these medications are Prandin® (repaglinide) and Starlix® (nateglinide).
- Repaglinide use in patients with CKD and ESRD may also require a dosage adjustment. An endocrinologist and nephrologist should determine an appropriate dose. Nateglinide is not recommended in patients with advanced kidney disease.
- Common side effects include changes in vision, dizziness, flu symptoms, headache,increased heartbeat, increased appetite, joint pain, nervousness, sweating, fatigue, tremors, upper respiratory tract infection and diarrhea.