Management of Diabetes in CKD

Choosing suitable therapies for patients with chronic kidney disease :

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

  1. Reduced renal gluconeogenesis (a major source of basal glucose output)
  2. Reduced renal clearance of both endogenous and exogenous insulin
  3. Impaired counter-regulatory response to hypoglycemia
Metformin• Do not initiate metformin below a GFR of 45
• Dose reduction and close monitoring for GFR 30-45
• Absolute contraindication below 30
SulfonylureasGlipizide 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

Glibenclamide and glyburide both undergo Hepatic Metabolism but are eliminated equally in bile and urine. Both drugs contraindicated in estimated GFR <60mL>
Glimepiride 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>
Gliclazide 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
MeglitinidesNateglinide (starlix) is hepatically metabolized with renal excretion of metabolites -- but not repaglinide (prandin)
Nateglinide should be used with caution in patients with advanced renal disease. (60mg with meals)
Repaglinide is safe until GFR is <30mL>
Alpha glucosidase inhibitors• Acarbose is almost entirely metabolized in the gastrointestinal tract. Less than 2% of the active drug or its metabolites are present in the urine.
• Miglitol is absorbed systemically and excreted unchanged in the urine.
• Modest efficacy in glycemic control and lack of long term trials in patients with kidney disease. Avoid in patients with CKD IV and V.
• Avoid if GFR <30
Thiazolidinediones• Pharmacokinetic profile of pioglitazone is similar between healthy subjects and patients with moderately or severely impaired renal function who do not require dialysis.
• Cause significant fluid retention as such should be used with caution in patients with heart failure and CKD and a significant reduction in GFR.
• No dose adjustment is required
DPP4 inhibitorsThere is structural heterogeneity with varying PK-PD profiles for this class.
• Sitagliptin is mainly excreted unchanged in the urine.
• Vildagliptin is metabolized mainly in the kidneys into inactive metabolites. 25% excreted unchanged in the urine.
• Saxagliptin is metabolized mainly in the liver into an active metabolite that is eliminated in the urine.
• Linagliptin 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.

Dose adjustments
Sitagliptin (100mg daily if GFR <50, 50mg daily if 30-50, 25mg daiy if GFR <30)
Saxagliptin 5mg daily if GFR >50, 2.5mg daily if GFR <50
Linagliptin -- No dose adjustment
GLP-1 agonistsGlucagon-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

DPP-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


  • Betônico, C. C., Titan, S. M., Correa-Giannella, M. L., Nery, M., & Queiroz, M. (2016). Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control. Clinics (Sao Paulo, Brazil), 71(1), 47–53.
  • Hahr, A.J., Molitch, M.E. Management of diabetes mellitus in patients with chronic kidney disease. Clin Diabetes Endocrinol 1, 2 (2015).
  • Fu, H., Liu, S., Bastacky, S. I., Wang, X., Tian, X. J., & Zhou, D. (2019). Diabetic kidney diseases revisited: A new perspective for a new era. Molecular metabolism, 30, 250–263.

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