From the Guidelines
The most appropriate intervention for this patient is to continue canagliflozin until the eGFR falls below 20 mL/min/1.73 m² or until dialysis is initiated or a kidney transplant is required. According to current guidelines, SGLT2 inhibitors like canagliflozin can be continued in patients with CKD until the eGFR drops below 20 mL/min/1.73 m² or until dialysis is initiated or a kidney transplant is required, as stated in the 2022 ADA and KDIGO consensus report 1. This recommendation is based on evidence that SGLT2 inhibitors provide significant cardiorenal protection in patients with CKD and diabetes, even as kidney function declines, as noted in the study published in Diabetes Care 1. The patient's current eGFR of 22 mL/min/1.73 m² is still above this threshold, and the presence of albuminuria (UACR 320 mg/g) further supports continuing the medication due to its proven benefits in reducing albuminuria and slowing CKD progression. Some key points to consider in this decision include:
- The patient's glycemic control is adequate with an HbA1c of 6.8%, which is within the target range for patients with diabetes and CKD.
- The combination of canagliflozin with liraglutide provides complementary mechanisms for managing both diabetes and kidney disease, as liraglutide has been shown to have beneficial effects on kidney function and cardiovascular outcomes in patients with CKD, as discussed in the Endocrine Reviews article 1.
- Discontinuing canagliflozin and initiating linagliptin or extended-release exenatide may not provide the same level of cardiorenal protection as continuing canagliflozin, and may also increase the risk of adverse events, such as hypoglycemia or gastrointestinal reactions.
- The patient's kidney function should be closely monitored, and the dose of canagliflozin should be adjusted as needed to minimize the risk of adverse events, as recommended in the Kidney International article 1.
From the FDA Drug Label
Not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m 2 The patient's current eGFR is 22 mL/min/1.73 m2, which is less than 30 mL/min/1.73 m2.
- The most appropriate intervention is to discontinue canagliflozin due to the patient's eGFR being below the recommended threshold 2.
- No alternative medication is recommended in the provided drug labels.
From the Research
Patient's Current Condition
The patient is a 66-year-old man with chronic kidney disease (CKD), hypertension, and type 2 diabetes (T2D). He has been on canagliflozin 100 mg orally daily for 6 months, along with other medications including atorvastatin, liraglutide, and lisinopril. His current laboratory values show an HbA1c of 6.8%, an estimated glomerular filtration rate (eGFR) of 22 mL/min/1.73 m2, and a urine albumin-to-creatinine ratio (UACR) of 320 mg/g.
Appropriate Intervention
Based on the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) consensus report, the following interventions are considered:
- Continue canagliflozin until the eGFR falls below 20 mL/min/1.73 m2
- Continue canagliflozin until dialysis is initiated or a kidney transplant is required
- Discontinue canagliflozin and initiate linagliptin
- Discontinue canagliflozin and initiate extended-release exenatide 2 mg once every 7 days
Evidence-Based Recommendations
Studies have shown that canagliflozin reduces renal and cardiovascular events in patients with T2D and CKD 3, 4. The CREDENCE trial demonstrated that canagliflozin safely reduced the risk of renal and cardiovascular events, with consistent results across eGFR subgroups, including those with an eGFR of 30 to <45 mL/min/1.73 m2 3. A post hoc analysis of the CREDENCE trial found that canagliflozin slowed the progression of kidney disease, without increasing acute kidney injury (AKI), even in participants with an eGFR <30 mL/min/1.73 m2 4.
Key Findings
- Canagliflozin reduces renal and cardiovascular events in patients with T2D and CKD 3, 4
- Canagliflozin slows the progression of kidney disease, without increasing AKI, even in participants with an eGFR <30 mL/min/1.73 m2 4
- The benefits of canagliflozin are consistent across eGFR subgroups, including those with an eGFR of 30 to <45 mL/min/1.73 m2 3
Recommended Course of Action
Based on the evidence, it is recommended to continue canagliflozin until the eGFR falls below 20 mL/min/1.73 m2 or until dialysis is initiated or a kidney transplant is required, as canagliflozin has been shown to reduce renal and cardiovascular events in patients with T2D and CKD, even in those with an eGFR <30 mL/min/1.73 m2 3, 4.