Can I safely start an angiotensin‑receptor blocker (ARB) such as losartan together with a sodium‑glucose co‑transporter‑2 (SGLT2) inhibitor such as empagliflozin in a patient with type 2 diabetes, hypertension and chronic kidney disease, and what are the recommended dosing and monitoring guidelines?

Combining ARBs with SGLT2 Inhibitors in Type 2 Diabetes with Hypertension and CKD

Yes, you can and should safely start losartan together with empagliflozin in this patient—this combination is explicitly recommended by the highest-quality guidelines and provides additive cardiovascular and renal protection beyond either agent alone. 1

Why This Combination Is Recommended

The KDIGO 2022 guideline issues a Grade 1A recommendation (highest level of evidence) to treat patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m² with an SGLT2 inhibitor, and a Grade 1B recommendation to initiate an ARB in patients with diabetes, hypertension, and albuminuria. 1 These are independent, complementary therapies that work through different mechanisms and should both be used simultaneously. 1, 2

• ARBs block the renin-angiotensin system to reduce intraglomerular pressure and proteinuria, slowing CKD progression. 1, 3
• SGLT2 inhibitors reduce cardiovascular death, heart failure hospitalization, and kidney disease progression through volume contraction, tubuloglomerular feedback activation, and metabolic effects independent of glucose lowering. 1, 2, 4
• Combination therapy produces greater blood pressure reduction (15 mmHg systolic) than either agent alone (8 mmHg for empagliflozin, 12 mmHg for losartan), with additive renal protection. 5, 6

Dosing Protocol

ARB Initiation and Titration

• Start losartan 50 mg once daily, then uptitrate to 100 mg once daily within 2–4 weeks if blood pressure remains above target (<130/80 mmHg) and the medication is tolerated. 1, 3, 7
• The renoprotective benefit of ARBs is dose-dependent; maximal doses used in landmark trials (losartan 100 mg daily, irbesartan 300 mg daily) should be the target. 1, 3

SGLT2 Inhibitor Initiation

• Start empagliflozin 10 mg once daily; this fixed dose is used for cardiovascular and renal protection and does not require titration. 1, 2
• Empagliflozin can be initiated at eGFR ≥20 mL/min/1.73 m² and should be continued even if eGFR subsequently falls below this threshold, unless dialysis is initiated or the drug is not tolerated. 1, 2

Pre-Initiation Assessment

Volume Status Evaluation

• Before starting empagliflozin, assess for volume depletion risk: review concurrent diuretic use, check for orthostatic hypotension, and consider reducing thiazide or loop diuretic doses by 50% to prevent symptomatic hypotension. 1, 2
• SGLT2 inhibitors cause predictable modest volume contraction (3–5 mmHg systolic BP reduction); this is therapeutic but requires monitoring in patients already on diuretics. 2, 6, 8

Baseline Laboratory Requirements

• Measure eGFR, serum potassium, serum creatinine, and urinary albumin-to-creatinine ratio before initiating either medication. 1, 2
• Confirm the patient is not pregnant or breastfeeding (absolute contraindication to both ARBs and SGLT2 inhibitors). 1, 2

Monitoring Schedule

First 2–4 Weeks After Initiation

• Recheck serum creatinine, eGFR, and potassium 2–4 weeks after starting or uptitrating the ARB or after starting empagliflozin. 1, 2
• Continue both medications unless serum creatinine rises >30% within 4 weeks of ARB initiation (suggesting acute kidney injury, volume depletion, or renal artery stenosis) or potassium exceeds 5.5 mmol/L despite medical management. 1
• A transient eGFR decline of 3–5 mL/min/1.73 m² after starting empagliflozin is expected hemodynamic adaptation and is not an indication to discontinue therapy. 1, 2

Ongoing Monitoring

• Reassess blood pressure at each visit; target <130/80 mmHg. 1, 7
• Measure eGFR and potassium every 3–6 months once stable. 1, 2
• Monitor urinary albumin-to-creatinine ratio every 6–12 months to assess treatment response. 1, 2

Managing Hyperkalemia Without Stopping the ARB

Hyperkalemia associated with ARB use can and should be managed medically before reducing or discontinuing the ARB, because the renal and cardiovascular benefits of continued RAS blockade outweigh the risks of mild-to-moderate hyperkalemia. 1

Step-Wise Hyperkalemia Management

1. Review and discontinue potassium-sparing diuretics, NSAIDs, and potassium supplements. 1
2. Restrict dietary potassium intake to <2–3 g/day. 1, 7
3. Correct volume depletion with increased diuretic dosing (thiazide or loop diuretic). 1
4. Add sodium bicarbonate 650 mg twice daily if metabolic acidosis is present (serum bicarbonate <22 mmol/L). 7
5. Consider gastrointestinal potassium binders (patiromer or sodium zirconium cyclosilicate) if potassium remains 5.5–6.0 mmol/L. 7
6. Only reduce or discontinue the ARB if potassium remains >5.5 mmol/L despite these measures or if symptomatic hypotension develops. 1, 7

Safety Precautions and Patient Education

SGLT2 Inhibitor-Specific Warnings

• Instruct the patient to temporarily discontinue empagliflozin during acute illness, prolonged fasting, or ≥3 days before surgery to prevent euglycemic diabetic ketoacidosis (DKA). 1, 2
• Educate about genital mycotic infection symptoms (the most common side effect) and advise proper genital hygiene. 2
• Counsel on volume depletion symptoms (dizziness, lightheadedness, weakness) and instruct the patient to increase fluid intake during hot weather or exercise. 1, 2

ARB-Specific Warnings

• Advise contraception in women of childbearing potential; discontinue the ARB immediately if pregnancy occurs. 1
• Do not combine losartan with an ACE inhibitor or direct renin inhibitor (aliskiren)—dual RAS blockade increases hyperkalemia, hypotension, and acute kidney injury without added benefit. 1, 3

Expected Clinical Benefits

Combination therapy with empagliflozin and losartan produces greater reductions in systolic blood pressure (−15 mmHg), albuminuria (−30%), and cardiovascular events than either agent alone. 5, 6

• Empagliflozin reduces the composite of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51–0.72). 4
• Losartan reduces the risk of doubling serum creatinine by 25% and progression to ESRD by 29% in type 2 diabetic nephropathy. 3
• The combination reduces cardiovascular death or heart failure hospitalization by 29% (HR 0.71,95% CI 0.55–0.92) and all-cause mortality by 31% (HR 0.69,95% CI 0.53–0.88). 2, 4

Common Pitfalls to Avoid

• Do not withhold empagliflozin solely because the patient has baseline hypotension; first optimize volume status by reducing diuretic doses. 2
• Do not discontinue empagliflozin if eGFR falls 3–5 mL/min/1.73 m² in the first month; this decline is expected and predicts long-term renal benefit. 1, 2
• Do not stop the ARB for mild hyperkalemia (potassium 5.0–5.5 mmol/L); employ medical management strategies first. 1, 7
• Do not delay uptitrating losartan to 100 mg daily; the maximal renoprotective dose is often underutilized in clinical practice. 1, 3, 7
• Do not add an ACE inhibitor to losartan or combine with aliskiren; dual RAS blockade is potentially harmful. 1