By Tracy Tylee, MD - 8th Nov 2018 - Course previews

Altering diabetes management in renal disease

In this video, we'll cover the factors you'll need to consider when managing diabetes in the context of renal impairment and describe the adjustments that may be necessary.

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TRANSCRIPT

[00:00:00] Diabetes is one of the leading causes of chronic kidney disease, thus, we often have to take declining renal function into consideration when adjusting our patient’s medications. Many diabetes medications need a decrease in dose as kidney function declines, since they're renally cleared and drug levels may accumulate with declining renal function. Patients with declining renal function are also at greater risk of hypoglycemia, due to decreased insulin clearance. So, treatment targets [00:00:30] may need to be adjusted as well.

 

Metformin is one of the mainstays of treatment for patients with type 2 diabetes and metformin is renally cleared, so as renal function declines, metformin levels can accumulate. This increase is concern for metabolic acidosis. Current recommendations are to discontinue metformin if GFR is less than 30 with a dose decrease for GFR between 30 and 45. Metformin is considered safe to use at full dose for GFR over 45, although renal function should be monitored [00:01:00] more closely, checking the creatinine every three to six months.

 

Sulfonylureas stimulate the pancreas to release insulin. Sulfonylureas are also renally cleared, so duration of action may be prolonged with renal dysfunction. This increases the risk of hypoglycemia, particularly with glyburide, which is metabolized to an active metabolite, so duration of action is longer than the other sulfonylureas. If you do use a sulfonylurea in renal dysfunction, you should up for glipizide or glimepiride, which have a lower risk for hypoglycemia. [00:01:30] You should also consider decreasing the dose, to minimize the risk of low blood sugars.

 

The DPP-4 inhibitors are another class of medication that are renally cleared, with the exception of linagliptin. Linagliptin is not extensively metabolized and is primarily excreted in the feces so it's safe to use in renal dysfunction. The other medications in this class do need dose adjustments as renal function declines. There is limited data regarding the use of the GLP-1 receptor agonists in renal disease, although albiglutide does not require [00:02:00] dose adjustment and is likely safe to use. Exenatide is not recommended for use in chronic kidney disease stage four or five. TZDs are not renally cleared, so theoretically it would be safe to use in renal dysfunction without any dose adjustments. However, given the side effects of the TZDs including fluid retention and osteoporosis, both of which can be significantly worse with chronic kidney disease, they should generally be avoided in patients with advanced  CKD.

 

The SGLT-2 inhibitors are not effective in patients with significant [00:02:30] chronic kidney disease. Since the mechanism of this medication depends on normal renal filtration, they're not likely to provide significant benefit with GFR less than 45 and are not recommended for patients with significant renal impairment. The safest option for most patients with advanced kidney disease is insulin. Insulin is renally cleared, so when  compared to those with normal kidney function, there's a longer duration of action in chronic kidney disease. But with appropriate dose adjustments, you can avoid hypoglycemia [00:03:00] and maintain good glucose control.

 

Overall, with changes in renal function, medications that are renally cleared such as metformin, most DPP-4 inhibitors, and some GLP-1 receptor agonists will need dose adjustments to maintain levels in the  therapeutic range. Other medications such as sulfonylureas and insulin will likely need dose adjustments to decrease the risk of hypoglycemia. For patients with CKD, it's important to reevaluate their diabetes treatments as kidney disease worsens, to ensure their regimens are safe [00:03:30] and appropriate.