Is gliclazide (sulfonylurea) suitable for patients with Chronic Kidney Disease (CKD) and diabetes?

Gliclazide in Chronic Kidney Disease and Diabetes

Gliclazide is a preferred sulfonylurea for patients with chronic kidney disease (CKD) and diabetes as it does not require dose adjustment in renal impairment and has a lower risk of hypoglycemia compared to other sulfonylureas.

Sulfonylureas in CKD: Safety Considerations

Sulfonylureas require careful consideration in patients with CKD due to:

• Increased risk of hypoglycemia in renal impairment due to:
  • Decreased drug clearance
  • Impaired renal gluconeogenesis 1
  • Altered pharmacokinetics in reduced GFR 2

Sulfonylurea Selection in CKD

Not all sulfonylureas are created equal when it comes to renal safety:

• Gliclazide: Preferred option in CKD

  • Does not require dose adjustment in renal impairment
  • Lower risk of hypoglycemia compared to other sulfonylureas
  • Safer pharmacokinetic profile in reduced renal function

• Glipizide: Second choice for CKD

  • No active metabolites
  • Not dependent on kidney elimination
  • Safer option for patients with kidney disease 3

• Glyburide/Glibenclamide: Should be avoided in CKD

  • Active metabolites accumulate in renal impairment
  • Significantly increased risk of hypoglycemia 3

Treatment Algorithm for Diabetes in CKD

Based on the 2022 ADA/KDIGO consensus report and 2020 KDIGO guidelines, the recommended treatment sequence for patients with T2D and CKD is:

1. First-line: Metformin (if eGFR ≥30 ml/min/1.73m²) 1
2. Second-line: SGLT2 inhibitor (if eGFR ≥30 ml/min/1.73m²) 1
3. Third-line: GLP-1 receptor agonist (particularly those with proven cardiovascular benefits) 1
4. Fourth-line: Consider other agents including sulfonylureas like gliclazide

Monitoring and Dose Considerations

When using gliclazide in CKD:

• Regular monitoring of renal function (every 3-6 months in moderate-severe CKD)
• Monitor for hypoglycemia, especially when initiating therapy
• Consider starting at a lower dose in advanced CKD
• Be cautious with drug interactions that may potentiate hypoglycemic effects

Special Considerations

• In advanced CKD (eGFR <30 ml/min/1.73m²), insulin or certain DPP-4 inhibitors may be preferred over sulfonylureas due to hypoglycemia risk 1
• If using sulfonylureas in advanced CKD, gliclazide would be the safest option
• For patients on dialysis, insulin remains the mainstay of treatment, though some sulfonylureas like gliclazide may be used with caution 4

Common Pitfalls to Avoid

1. Inappropriate sulfonylurea selection: Not all sulfonylureas are suitable for CKD. Avoid glyburide/glibenclamide in renal impairment.

2. Inadequate monitoring: Failure to regularly assess renal function and adjust therapy accordingly.

3. Overlooking hypoglycemia risk: Patients with CKD are at higher risk of hypoglycemia, requiring more frequent blood glucose monitoring.

4. Neglecting medication review: Many patients with CKD receive inappropriate medications or doses. A study found approximately 21% of patients with severe CKD were inappropriately receiving metformin 5.

5. Missing newer therapeutic options: SGLT2 inhibitors and GLP-1 receptor agonists have demonstrated cardiovascular and renal benefits and should be considered before sulfonylureas when appropriate 1.

In conclusion, while gliclazide is a suitable option for patients with diabetes and CKD, current guidelines recommend prioritizing metformin (if eGFR permits), SGLT2 inhibitors, and GLP-1 receptor agonists before considering sulfonylureas due to their proven cardiovascular and renal benefits.