There has been a large amount of research done on a variety of conditions in the healthcare field; however, as long as obesity continues to plague this country, diabetes will continue to be a significant issue. Almost everyone knows somebody with diabetes and, while in the past diabetes was managed by endocrinologists, its ubiquity means that healthcare providers at all levels need to be well-versed in its management.
According to information recently published by the United States Renal Data System, the National Kidney Foundation estimates that about 15% of all Americans (about 30 million people) suffer from some form of chronic kidney disease (CKD). In close to half of these cases, the original cause is diabetes. Because numerous studies have demonstrated that a reduction in hemoglobin A1c (HgbA1c) can reduce the severity of microvascular complications caused by diabetes, it is important for healthcare providers to take steps to reduce their patients’ HgbA1c levels to both treat and prevent diabetic nephropathy.
Overview: Types of Anti-Hyperglycemic Agents
The world of diabetes has been changed by the rapid pace of research, which has led to the development of a wide variety of diabetes medications. A recently updated set of guidelines on the treatment of patients with diabetic nephropathy appears in The Journal of Nurse Practitioners. It is important to understand how these medications work so that they can be used in the right situation. As Maxson and Lisenby outline in that guideline, some of these include:
Metformin remains the first-line medication in the treatment of diabetes. It increases insulin sensitivity to provide a reduction in A1c. It does this by reducing gluconeogenesis in the liver, reducing glucose absorption in the digestive tract, and increasing the use of glucose in the body.
In patients who have diabetic nephropathy, metformin needs to be watched closely. When the GFR drops under 45, the dose may need to be reduced by 50%. It should not be started in individuals with a GFR under 45, but can be continued. Once the GFR drops under 30, metformin needs to be stopped.
These agents help reduce blood glucose by helping the body release its own insulin from the pancreatic beta cells. Remember that these agents can cause a dangerously low blood sugar, particularly in those with kidney damage. If the kidneys are damaged, they cannot filter out this class of medication as quickly and an overdose could occur. Particularly in elderly individuals and those who are also using insulin, blood glucose needs to be watched closely.
In individuals with diabetic nephropathy, the first-line sulfonylurea is Glucotrol. DiaBeta should not be used at all and Amaryl needs to be dosed carefully, starting at 1 mg daily. Low blood glucose can lead to seizures and death.
Thiazolidinediones, such as pioglitazone and rosiglitazone, are commonly used in the treatment of diabetes. These agents reduce the glucose produced by the liver and increase the use of glucose in the periphery. This helps to reduce HgbA1c. This class of medications is metabolized completely by the liver. Therefore, it does not need to be reduced in individuals who have diabetic nephropathy. On the other hand, these medications can cause fluid retention. Combined with the fluid retention that already happens in patients with diabetic nephropathy, this can lead to heart failure. Therefore, this class of medications is not preferred in individuals with diabetic nephropathy.
Many clinicians associate insulin dependence with Type 1 Diabetes; however, many individuals with Type 2 Diabetes also eventually wind up on insulin. Because of this, it is important to dose insulin properly. There are lots of different formulations of insulin, including both endogenous insulin and exogenous. While endogenous insulin is broken down by the liver, exogenous insulin is secreted by the kidneys. Many types of insulin are made up of both types and, therefore, the pharmacokinetics of these medications are hard to adjust; however, in CKD patients, the dose should be reduced. The exact nature of this reduction needs to be handled on a case-by-case basis.
- Other Classes
- Of the DPP-4 inhibitors, Linagliptin does not require a dose adjustment and is preferred. Saxagliptin and Sitagliptin all require dose adjustments.
- For patients on GLP-1 inhibitors, Liraglutide and Dulaglutide do not require a dose adjustment and are preferred. The other medications in this class have limited data or have dose restrictions.
- Most SGLT-2 inhibitors have restrictions in individuals with a GFR under 60 and are contraindicated in individuals with a GFR under 45.
It is important to properly manage the medications of people with diabetes to prevent serious complications. This includes chronic kidney disease and diabetic nephropathy, a common complication that could lead to death. Note that some of these medications, such as liraglutide and empagliflozin, also confer a cardiovascular benefit. Finally, it is vital to remember that medications that are excreted by the kidney will need to be monitored carefully in individuals who have a reduced GFR, such as those with chronic kidney disease. It is important that you regularly monitor the kidney function of your patients with diabetes to ensure that they are kept safe.
For more information
- American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018. Diabetes Care. 2018;l41(Suppl 1):S73-S85.
- Marso SP, Daniels GH, Brown-Frandsen K, et al/. Liraglutide and cardiovascular outcomes in Type 2 Diabetes. N Engl J Med. 2016;375(4):311-322.
- Muller C, Dimitrov Y, Imhoff O. Oral antidiabetics use among diabetic type 2 patients with chronic kidney disease. Do nephrologists take account of recommendations? J Diabetes Complications. 2016;May-June;30(4):675-680.
- Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. 2011;Jun;34(6):1431-1437.
Last updated on 9/25/19.