Use of Hypoglycemic Agents in CKD

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Maintaining adequate glycemic control in patients with diabetic kidney disease can be a challenge.  First, it is hypothesized that worsened glycemic control will lead to a greater tendency towards diabetic nephropathy.  Second, individuals with more advanced CKD are more likely to suffer from hypoglycemia.  Finally, many of the drugs which are so useful in maintaining good glycemic control are partially cleared by the kidney, making their use problematic in those with advanced or fluctuating renal disease.  Here is a brief list of some of the medications used to control hyperglycemia and their caveats unique to CKD.

1.  insulin:  insulin is mainly cleared by the kidney; thus, it is not uncommon for patients with diabetic nephropathy to note that their insulin requirements gradually go down as their kidney function gets worse.  Insulin dose must usually therefore be decreased once the GFR dips below 50 mL/min.  
2.  sulfonylureas:  some of these drugs have metabolites which are normally excreted by the kidney which retain secretogogue activity and therefore may cause hypoglycemia in patients with reduced GFR (e.g., CKD 3 or above).  Glyburide and glimeperide are the two main offenders here.  According to KDOQI guidelines, it is okay to use glipizide or gliclazide, which are listed as “preferred sulfonylureas”.  
3.  Metformin:  although one of the cheapest and most effective glucose-lowering medications, there are many who believe that metformin should be avoided in advanced CKD (e.g., stages 3-5) based on a risk of lactic acidosis.  This guy, however, disagrees with that assertion. 
4.  thiazolidinediones:  e.g., rosiglitazone, pioglitazone are generally considered safe for patients with CKD in that they are not renally excreted.  However, this class of medications may result in fluid retention which can be an issue in those who are susceptible to edema.  
5.  the “glinides”:  this newer class of drugs to treat hyperglycemia includes nateglinide (which should be avoided since an active metabolite is excreted by the kidney) and rapaglinide & mitiglinide, which are considered okay to use in patients with CKD without an adjustment necessary.
6.  incretin-based insulin secretagogues:  this newer class of drugs I personally have never used includes excenatide (which KDOQI says is okay to use) and sitagliptin (which KDOQI recommends a dose reduction by 75%).  
7.  alpha-glucosidase inhibitors:  both acarbose and miglitol are to be avoided in patients with Cr > 2. 

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