{"id":989607,"date":"2022-02-21T06:00:00","date_gmt":"2022-02-21T11:00:00","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/?p=989607"},"modified":"2023-03-16T05:45:53","modified_gmt":"2023-03-16T10:45:53","slug":"management-of-diabetes-in-ckd","status":"publish","type":"post","link":"https:\/\/myendoconsult.com\/learn\/management-of-diabetes-in-ckd\/","title":{"rendered":"Management of Diabetes in CKD"},"content":{"rendered":"

Choosing suitable therapies for patients with chronic kidney disease :<\/h2>\n

Patients with diabetes and chronic kidney disease (CKD) require a modification of medical therapy. CKD increases the risk of hypoglycemia due to various reasons.<\/p>\n

    \n
  1. Reduced renal gluconeogenesis (a major source of basal glucose output)<\/li>\n
  2. Reduced renal clearance of both endogenous and exogenous insulin<\/li>\n
  3. Impaired counter-regulatory response to hypoglycemia<\/li>\n<\/ol>\n\n\n\n\n\t\n\t\n\t\n\t\n\t\n\t\n\t\n\t
    Drug<\/td>Comments<\/td>\n<\/tr>\n
    Metformin<\/td>\u2022\tDo not initiate metformin below a GFR of 45
    \n\u2022\tDose reduction and close monitoring for GFR 30-45
    \n\u2022\tAbsolute contraindication below 30
    \n<\/td>\n<\/tr>\n
    Sulfonylureas<\/td>Glipizide undergoes Hepatic Metabolism into several inactive metabolites; as such, its clearance and elimination half-life is not affected by a reduction in the estimated GFR. It is the sulfonylurea of choice in CKD
    \n
    \nGlibenclamide and glyburide both undergo Hepatic Metabolism but are eliminated equally in bile and urine. Both drugs contraindicated in estimated GFR <60mL\/min
    \n
    \nGlimepiride undergoes Hepatic Metabolism into two primary metabolites, one of which has significant hypoglycemic potential. In CKD, the metabolites may accumulate. Glimepiride causes less hypoglycemia than glyburide. contraindicated in estimated GFR <60mL\/min
    \n
    \nGliclazide has inactive metabolites that are eliminated mainly in the urine (80%) and presents a lower risk of hypoglycemia than glibenclamide and glimepiride. Pay particular attention to dose and avoid if GFR falls below 40
    \n<\/td>\n<\/tr>\n
    Meglitinides<\/td>Nateglinide (starlix) is hepatically metabolized with renal excretion of metabolites -- but not repaglinide (prandin)
    \nNateglinide should be used with caution in patients with advanced renal disease. (60mg with meals)
    \nRepaglinide is safe until GFR is <30mL\/min\/1.73m2 (0.5mg with meals)<\/td>\n<\/tr>\n
    Alpha glucosidase inhibitors<\/td>\u2022\tAcarbose is almost entirely metabolized in the gastrointestinal tract. Less than 2% of the active drug or its metabolites are present in the urine.
    \n\u2022\tMiglitol is absorbed systemically and excreted unchanged in the urine.
    \n\u2022\tModest efficacy in glycemic control and lack of long term trials in patients with kidney disease. Avoid in patients with CKD IV and V.
    \n\u2022\tAvoid if GFR <30
    \n<\/td>\n<\/tr>\n
    Thiazolidinediones<\/td>\u2022\tPharmacokinetic profile of pioglitazone is similar between healthy subjects and patients with moderately or severely impaired renal function who do not require dialysis.
    \n\u2022\tCause significant fluid retention as such should be used with caution in patients with heart failure and CKD and a significant reduction in GFR.
    \n\u2022\tNo dose adjustment is required
    \n<\/td>\n<\/tr>\n
    DPP4 inhibitors<\/td>There is structural heterogeneity with varying PK-PD profiles for this class.
    \n\u2022\tSitagliptin is mainly excreted unchanged in the urine.
    \n\u2022\tVildagliptin is metabolized mainly in the kidneys into inactive metabolites. 25% excreted unchanged in the urine.
    \n\u2022\tSaxagliptin is metabolized mainly in the liver into an active metabolite that is eliminated in the urine.
    \n\u2022\tLinagliptin is the only DPP-4 inhibitor that is eliminated entirely via the biliary system. This is the agent of choice in patients in all stages of kidney failure, without any dose adjustments.
    \n
    \nDose adjustments
    \nSitagliptin (100mg daily if GFR <50, 50mg daily if 30-50, 25mg daiy if GFR <30)
    \nSaxagliptin 5mg daily if GFR >50, 2.5mg daily if GFR <50
    \nLinagliptin -- No dose adjustment
    \n<\/td>\n<\/tr>\n
    GLP-1 agonists<\/td>Glucagon-like peptide 1 is an incretin produced from the PROGLUCAGON gene in L cells of the small intestine and is secreted in response to nutrients. It is deficient in patients with T2DM
    \n
    \nDPP-4 inhibitors inhibit DPP-4, which is a ubiquitous enzyme expressed on the surface of most cell types that deactivates GLP-1; therefore, its inhibition could potentially affect glucose regulation through multiple effects
    \n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n

    References<\/h2>\n