What are the typical dosages for canagliflozin (SGLT2 inhibitor), metformin, ACE (Angiotensin-Converting Enzyme) inhibitors, and ARBs (Angiotensin Receptor Blockers) in a patient with chronic kidney disease, hypertension, and diabetes type II?

Medication Dosages for CKD, Hypertension, and Type 2 Diabetes

SGLT2 Inhibitor: Canagliflozin

Start canagliflozin 100 mg once daily before the first meal of the day, regardless of current glycemic control, as long as eGFR ≥20 mL/min/1.73 m². 1

• The 100 mg dose is appropriate for patients with eGFR ≥20 mL/min/1.73 m², though glucose-lowering efficacy diminishes below eGFR 45 mL/min/1.73 m² 2, 3
• Continue canagliflozin even if eGFR falls below 20 mL/min/1.73 m² unless dialysis is initiated or the medication is not tolerated 1, 4
• The 300 mg dose can be considered if eGFR ≥60 mL/min/1.73 m² and additional glycemic control is needed, but kidney and cardiovascular protection occurs at both doses 3
• Canagliflozin reaches steady-state in 4-5 days with a half-life of 10.6-13.1 hours 3

Critical Monitoring for Canagliflozin

• Assess volume status before initiation; consider reducing thiazide or loop diuretic doses to prevent hypotension 1
• If patient is on insulin or sulfonylureas, reduce those doses by 10-20% when starting canagliflozin to prevent hypoglycemia 5
• Expect a reversible acute eGFR decline of up to 5 mL/min/1.73 m² within 2-4 weeks; this is hemodynamic and not a reason to discontinue 1, 6
• Withhold during prolonged fasting, surgery, or critical illness due to ketoacidosis risk 1

Metformin

Start metformin 500 mg twice daily with meals when eGFR ≥30 mL/min/1.73 m², titrating to a maximum of 2000 mg daily in divided doses. 2, 4

• When eGFR is 30-44 mL/min/1.73 m², reduce the maximum dose to 1000 mg daily 2, 4
• Discontinue metformin when eGFR falls below 30 mL/min/1.73 m² due to lactic acidosis risk 4, 5
• Temporarily hold metformin during acute illness, hospitalizations, or before procedures with iodinated contrast 5
• Monitor eGFR every 3-6 months to guide dose adjustments 5

ACE Inhibitors

Initiate an ACE inhibitor and titrate to the highest approved dose that is tolerated in patients with diabetes, hypertension, AND albuminuria. 1

Common starting and target doses:

• Lisinopril: Start 10 mg once daily, titrate to 40 mg once daily 4
• Enalapril: Start 5 mg once daily, titrate to 20 mg twice daily
• Ramipril: Start 2.5 mg once daily, titrate to 10 mg once daily

ACE Inhibitor Monitoring Algorithm

• Check serum creatinine and potassium within 2-4 weeks after starting or increasing dose 1
• Continue therapy if creatinine rises <30% from baseline 1
• If creatinine rises >30% within 4 weeks: Review for acute kidney injury causes, assess volume status, check for renal artery stenosis, and reassess concomitant medications (NSAIDs, diuretics) 1
• For hyperkalemia (K+ >5.5 mEq/L): First attempt potassium management with dietary restriction, diuretics, sodium bicarbonate, or GI cation exchangers before reducing ACE inhibitor dose 1
• Reduce dose or discontinue only for: Symptomatic hypotension, uncontrolled hyperkalemia despite medical management, or uremic symptoms with eGFR <15 mL/min/1.73 m² 1

Angiotensin Receptor Blockers (ARBs)

Use an ARB at the highest tolerated dose if ACE inhibitor is not tolerated (typically due to cough). 1

Common starting and target doses:

• Losartan: Start 50 mg once daily, titrate to 100 mg once daily 4
• Irbesartan: Start 150 mg once daily, titrate to 300 mg once daily
• Telmisartan: Start 40 mg once daily, titrate to 80 mg once daily

Critical ARB Considerations

• Never combine an ACE inhibitor with an ARB—this combination is potentially harmful 1
• Apply the same monitoring algorithm as ACE inhibitors (creatinine and potassium within 2-4 weeks) 1
• ARBs are contraindicated in pregnancy; advise contraception in women of childbearing potential 1

Blood Pressure Target

Target blood pressure <130/80 mmHg in patients with CKD, diabetes, and albuminuria. 4, 7

• ACE inhibitors or ARBs should be first-line when albuminuria is present 1
• Add dihydropyridine calcium channel blockers (amlodipine 5-10 mg daily) and/or diuretics (chlorthalidone 12.5-25 mg daily) if BP target not achieved with RAS blockade alone 1, 7
• All three classes (ACE/ARB, CCB, diuretic) are often needed to reach BP targets 1

Common Pitfalls to Avoid

• Do not stop SGLT2 inhibitors based solely on reduced glucose-lowering effect at lower eGFR—the primary benefit is cardiorenal protection, not glycemic control 5
• Do not immediately discontinue ACE inhibitors/ARBs for mild hyperkalemia or creatinine rise <30%—attempt medical management first 1
• Do not use ACE inhibitors and ARBs together—dual RAS blockade increases adverse events without additional benefit 1
• Do not continue metformin when eGFR <30 mL/min/1.73 m²—lactic acidosis risk outweighs benefits 4, 5