How should Invokana (canagliflozin) be initiated and monitored in a patient with coronary artery disease and type 2 diabetes who has an eGFR of at least 30 mL/min/1.73 m²?

Initiating and Monitoring Invokana in Patients with CAD and Type 2 Diabetes

Start canagliflozin 100 mg once daily before the first meal in patients with coronary artery disease and type 2 diabetes when eGFR is ≥30 mL/min/1.73 m², as SGLT2 inhibitors provide cardiovascular benefit in this population, with the 100 mg dose being the maximum recommended dose when eGFR is 30 to <60 mL/min/1.73 m² 1.

Rationale for Use in CAD

Patients with established atherosclerotic cardiovascular disease (including CAD) should receive an SGLT2 inhibitor or GLP-1 receptor agonist independent of baseline HbA1c or glycemic targets 2. While GLP-1 receptor agonists have the strongest evidence for MACE reduction in established ASCVD, SGLT2 inhibitors like canagliflozin provide consistent cardiovascular benefits including reduction in cardiovascular death and heart failure hospitalization 3, 2. Canagliflozin specifically reduced cardiovascular death or heart failure hospitalization by 30% (HR 0.70) across all levels of renal function and albuminuria in pooled analysis 4.

Dosing Algorithm by Renal Function

The dosing is straightforward and based solely on eGFR 1:

• eGFR ≥60 mL/min/1.73 m²: Start 100 mg daily; may increase to 300 mg daily for additional glycemic control
• eGFR 30 to <60 mL/min/1.73 m²: Maximum dose is 100 mg daily (do not increase to 300 mg)
• **eGFR <30 mL/min/1.73 m²**: Do not initiate (exception: patients already on therapy with albuminuria >300 mg/day may continue 100 mg for renal/cardiovascular protection)

Pre-Initiation Requirements

Before starting canagliflozin 3, 1:

1. Assess renal function - Obtain baseline eGFR
2. Correct volume depletion - Ensure adequate hydration status, particularly in elderly patients or those on diuretics
3. Review foot risk - Exercise caution in patients with prior amputation, severe peripheral arterial disease, or active diabetic foot ulcers (canagliflozin-specific concern) 3
4. Adjust concomitant medications:
   • If HbA1c is well-controlled or history of hypoglycemia: wean/stop sulfonylureas and consider reducing insulin by ~20%
   • May need to reduce diuretic dose if volume depletion risk exists

Critical Patient Education Points

Provide specific counseling on 3:

• Genital mycotic infections: Emphasize genital hygiene practices
• Volume depletion symptoms: Lightheadedness, orthostasis, weakness - instruct to hold medication if unable to maintain oral intake
• Euglycemic DKA: Nausea, vomiting, abdominal pain can occur even with glucose 150-250 mg/dL - seek urgent care if these develop
• Foot care: Report any foot wounds immediately, especially critical given CAD population often has concurrent peripheral vascular disease
• Surgical planning: Withhold at least 3 days before major surgery or prolonged fasting 1

Monitoring Schedule

First 4 weeks 3:

• Home glucose monitoring more frequently (especially if on insulin, sulfonylurea, or glinides)
• Watch for hypoglycemia and volume depletion symptoms

Ongoing monitoring:

• Renal function as clinically indicated (particularly important when initiating or up-titrating ACE inhibitors/ARBs) 3
• Assess for genital infections
• Monitor for foot complications

Special Considerations in CAD Population

The elderly CAD population requires particular attention 1:

• Patients ≥65 years have higher incidence of volume depletion-related adverse events (hypotension, postural dizziness, syncope, dehydration), especially with 300 mg dose
• Patients ≥75 years show even more prominent increases in these events
• This reinforces the importance of the 100 mg maximum dose when eGFR is 30-60 mL/min/1.73 m²

Renal Safety Profile

Despite theoretical concerns, canagliflozin demonstrated favorable renal safety in the CREDENCE trial 5. The drug reduced overall kidney-related adverse events by 29% (HR 0.71) and showed no increased risk of acute kidney injury across all eGFR strata. When AKI did occur, full recovery within 30 days was more frequent with canagliflozin (53.1% vs 35.4%) 5. Continue therapy even if eGFR falls below 20 mL/min/1.73 m² until dialysis or transplantation 6.

Drug Interactions

When co-administering with UGT enzyme inducers (rifampin, phenytoin, phenobarbital, ritonavir), increase dose based on renal function: up to 200 mg daily if eGFR ≥60, maximum 200 mg if eGFR <60 1.