Guidelines for Using Oral Hypoglycemic Agents in CKD
In patients with chronic kidney disease, second-generation sulfonylureas like glipizide and gliclazide are the preferred sulfonylureas due to their lack of active metabolites and lower risk of hypoglycemia, while metformin should be avoided in advanced CKD and first-generation sulfonylureas should be completely avoided. 1
General Considerations for OHAs in CKD
- Patients with decreased kidney function (CKD stages 3-5) have increased risks of hypoglycemia due to decreased clearance of insulin and oral agents, as well as impaired kidney gluconeogenesis 1
- Monitoring glycemic control using HbA1c twice yearly is reasonable, but accuracy declines with advanced CKD (G4-G5), particularly in dialysis patients 1
- Daily glycemic monitoring with continuous glucose monitoring or self-monitoring of blood glucose helps prevent hypoglycemia when using agents with hypoglycemia risk 1
- For patients with CKD who don't perform daily monitoring, glucose-lowering agents with lower hypoglycemia risk are preferred 1
Specific OHA Recommendations by Drug Class
Sulfonylureas
- First-generation sulfonylureas (chlorpropamide, tolazamide, tolbutamide) should be completely avoided in CKD due to increased half-lives and risk of hypoglycemia 1
- Second-generation sulfonylureas like glipizide and gliclazide are preferred in CKD as they don't have active metabolites 1, 2
- Gliclazide can be safely used even in CKD stage 4 (eGFR 15-29 ml/min/1.73m²) with appropriate dose adjustments 3
- Progressive decreases in kidney function necessitate decreased dosing of sulfonylureas to avoid hypoglycemia 1
Meglitinides
- Repaglinide is preferred over nateglinide in CKD as it doesn't have increased active metabolites with decreased kidney function 1
- Repaglinide is a suitable option for dialysis patients as it's rarely accompanied by hypoglycemia 4
- Caution is needed when combining repaglinide with gemfibrozil due to increased repaglinide concentrations and half-life 1
Biguanides
- Metformin should not be given to patients with serum creatinine ≥1.5 mg/dL in men and ≥1.4 mg/dL in women due to risk of lactic acidosis 1
- Metformin is contraindicated for moderate to advanced CKD 4, 5
Alpha-Glucosidase Inhibitors
- These agents are rarely accompanied by hypoglycemia 4
- However, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines recommend avoiding alpha-glucosidase inhibitors in advanced CKD and dialysis 4
Special Considerations for Dialysis Patients
- Insulin therapy remains the mainstay of treatment for diabetic patients with moderate to advanced CKD, particularly those on dialysis 4
- Patients on dialysis should consume between 1.0 and 1.2 g protein/kg/day 1
- Hypoglycemia risk increases during hemodialysis sessions, requiring careful monitoring and potential dose adjustments 6
- HbA1c may not be as representative of glycemic control in dialysis patients due to decreased metabolism, anemia, and shorter red cell life 1
Monitoring and Dose Adjustments
- Close monitoring of glucose levels is essential after initiating or adjusting doses of OHAs in CKD patients 1, 3
- Consider less stringent glycemic targets (HbA1c ~7.0%) for patients with advanced CKD who are at risk of hypoglycemia 3
- Insulin doses and oral hypoglycemic doses may change substantially during transition from earlier stages of CKD to dialysis 1
- During acute illness, surgery, or prolonged fasting, consider temporarily reducing or suspending hypoglycemic agents to prevent hypoglycemia 3
Pitfalls and Caveats
- Hypoglycemia risk is significantly increased in CKD due to decreased drug clearance and impaired renal gluconeogenesis 1
- Glucose contained in dialysate (especially peritoneal dialysate) may increase requirements for hypoglycemic agents 1
- Drug interactions can significantly affect hypoglycemia risk in CKD patients (e.g., repaglinide with gemfibrozil) 1, 3
- Recommended oral antidiabetic agents differ between countries, so local guidelines should be consulted 4