For an adult with type 2 diabetes currently taking sitagliptin 50 mg twice daily, what is the appropriate dosing regimen for Invokana (canagliflozin)?

Switching from Sitagliptin to Invokana: Dosing Guidance

For an adult with type 2 diabetes currently on sitagliptin 50 mg twice daily, discontinue the sitagliptin and initiate Invokana (canagliflozin) at 100 mg once daily before the first meal of the day, provided the eGFR is ≥45 mL/min/1.73 m².1

Understanding the Medication Classes

These are fundamentally different drug classes that cannot be "dose-converted" in the traditional sense:

• Sitagliptin is a DPP-4 inhibitor that works by increasing incretin levels, which stimulate insulin secretion and inhibit glucagon release, providing an HbA1c reduction of approximately 0.5–0.8%234
• Invokana (canagliflozin) is an SGLT2 inhibitor that works by blocking glucose reabsorption in the kidneys, causing glucose excretion in urine, and provides cardiovascular and renal protection beyond glucose lowering1

Invokana Initiation Protocol

Standard Starting Dose

• Start with 100 mg once daily taken before the first meal of the day for all indications (glycemic control, cardiovascular risk reduction, and renal protection)1
• This 100 mg dose provides full cardiovascular and renal benefits without requiring titration5

Renal Function Requirements (Critical)

• Do NOT initiate Invokana if eGFR <45 mL/min/1.73 m²15
• For patients with eGFR 30 to <60 mL/min/1.73 m², the maximum dose is 100 mg once daily1
• The glucose-lowering efficacy decreases with declining renal function, but cardiovascular and kidney benefits are preserved at lower eGFR levels5

Optional Dose Escalation (For Glycemic Control Only)

• If additional glycemic control is needed after tolerating 100 mg, the dose may be increased to 300 mg once daily1
• However, the 300 mg dose provides no additional cardiovascular or renal benefit beyond the 10 mg dose5
• This higher dose is only for glycemic optimization, not for cardio-renal protection5

Transitioning from Sitagliptin

Why the Switch May Be Beneficial

• SGLT2 inhibitors and GLP-1 receptor agonists are strongly preferred over DPP-4 inhibitors for patients with type 2 diabetes due to proven cardiovascular mortality and morbidity benefits67
• Invokana specifically reduces the risk of major adverse cardiovascular events (CV death, MI, stroke) in adults with established CVD1
• It also reduces the risk of ESKD, doubling of serum creatinine, CV death, and hospitalization for heart failure in patients with diabetic nephropathy (albuminuria >300 mg/day)1

Practical Transition Steps

1. Assess renal function before initiating Invokana—this is mandatory1
2. Correct volume depletion if present before starting Invokana1
3. Discontinue sitagliptin (no tapering needed for DPP-4 inhibitors)23
4. Start Invokana 100 mg once daily the following day1
5. Continue metformin at maximum tolerated dose (up to 2000–2550 mg daily) as foundational therapy8

Concomitant Medication Adjustments

If Patient Is on Sulfonylureas or Insulin

• Reduce or discontinue sulfonylureas/glinides if HbA1c is well-controlled or if the patient has frequent hypoglycemic events5
• For patients on insulin, maintain at least low-dose insulin when starting Invokana to reduce ketoacidosis risk5

If Patient Is on UGT Enzyme Inducers

• If co-administering with rifampin, phenytoin, phenobarbital, or ritonavir, increase Invokana to 200 mg once daily (if eGFR ≥60 mL/min/1.73 m²) or to a maximum of 200 mg once daily (if eGFR <60 mL/min/1.73 m²)1

Monitoring Requirements

• Check eGFR before initiation and as clinically indicated1
• Monitor for genital mycotic infections (occur in ~6% of patients vs. 1% on placebo)5
• Assess for urinary tract infections5
• Watch for signs of euglycemic ketoacidosis, especially in insulin-requiring patients5
• Reassess HbA1c at 3 months to evaluate glycemic response6

Critical Safety Considerations

Surgical Planning

• Withhold Invokana at least 3 days before surgery or procedures with prolonged fasting1
• Resume when the patient is clinically stable and has resumed oral intake1

Volume Depletion Risk

• Correct volume depletion before initiating Invokana, particularly in elderly patients (≥65 years) or those with renal impairment1

Ketoacidosis Prevention

• Daily hygienic measures may reduce the risk of genital mycotic infections5
• For insulin-dependent patients, maintaining at least low-dose insulin reduces ketoacidosis risk5

Common Pitfalls to Avoid

• Do NOT use the standard sitagliptin dose of 100 mg/day in patients with eGFR <60 mL/min/1.73 m² without dose adjustment (sitagliptin requires 50 mg once daily for moderate renal impairment and 25 mg once daily for severe renal impairment)910
• Do NOT initiate Invokana if eGFR <45 mL/min/1.73 m²—this is an absolute contraindication for starting therapy1
• Do NOT prioritize DPP-4 inhibitors over SGLT2 inhibitors in patients with established cardiovascular disease, heart failure, or chronic kidney disease, as this forfeits proven mortality and morbidity benefits67
• Do NOT assume dose equivalence—these are mechanistically distinct drug classes with different dosing paradigms12