Kidney Protection in Diabetes with SGLT2 Inhibitors and RAAS Blockade

Introduction to Guideline Recommendations

The American Diabetes Association recommends SGLT2 inhibitors as first-line therapy for all patients with diabetic kidney disease, in addition to ACE inhibitors or ARBs, as they reduce kidney failure, dialysis, or renal death by 30-40% even when added to maximum ACE inhibitor/ARB therapy 1

ACE inhibitors or ARBs remain essential for delaying progression of nephropathy in both hypertensive and normotensive diabetic patients through distinct mechanisms, reducing intraglomerular pressure and proteinuria independent of blood pressure effects 2, 3
The American College of Cardiology and other guideline societies support the use of ACE inhibitors/ARBs and SGLT2 inhibitors together for kidney protection in diabetes, as they work through complementary mechanisms 1, 2

Start ACE inhibitor or ARB in all patients with diabetes and albuminuria (UACR ≥30 mg/g), regardless of blood pressure status, and start SGLT2 inhibitor simultaneously in all patients with diabetic kidney disease, regardless of baseline glucose control 1, 2
Titrate ACE inhibitor or ARB to maximum tolerated dose approved for hypertension treatment, and monitor serum creatinine and potassium within 2-4 weeks of initiation or dose changes 2, 4

Annual UACR testing to guide therapy intensity and track treatment response, and serum creatinine at least annually to estimate GFR and stage CKD progression 1
Potassium monitoring within 2-4 weeks of ACE inhibitor/ARB initiation or dose changes, as both ACE inhibitors/ARBs and potential future addition of finerenone increase hyperkalemia risk 1, 2

Never discontinue ACE inhibitor/ARB when starting empagliflozin, as this eliminates proven renoprotective benefits that are mechanistically distinct from SGLT2 inhibition 1, 5
Never combine ACE inhibitor with ARB, as dual RAAS blockade increases adverse events without additional cardiovascular or kidney benefits 1, 2, 4

Target blood pressure <130/80 mmHg for patients with diabetic kidney disease and albuminuria ≥30 mg/24 hours, and target HbA1c as close to 7% as safely possible without causing hypoglycemia to reduce risk and slow progression of diabetic kidney disease 1