Combination of ARBs and SGLT2 Inhibitors for Slowing CKD Progression in Diabetic Patients
The combination of an angiotensin receptor blocker (ARB) and a sodium-glucose cotransporter 2 (SGLT2) inhibitor is highly effective in slowing the progression of chronic kidney disease in patients with diabetes, providing superior renoprotection compared to either agent alone. 1
Mechanism of Action and Complementary Effects
- ARBs work by blocking the renin-angiotensin-aldosterone system (RAAS), reducing intraglomerular pressure, proteinuria, and inflammatory/fibrotic processes in the kidney 2
- SGLT2 inhibitors provide renoprotection through multiple mechanisms independent of glycemic control, including:
Evidence for Combination Therapy
Meta-analysis data shows that combination therapy with SGLT2 inhibitors and RAAS blockers (including ARBs) produces significant improvements compared to RAAS blockers alone 1:
- Reduction in systolic blood pressure (-3.84 mmHg)
- Reduction in diastolic blood pressure (-1.06 mmHg)
- Reduction in urine albumin:creatinine ratio (-29.70%)
- Improvements in glycemic control (HbA1c and fasting plasma glucose)
The combination provides additive renoprotective effects by targeting different pathophysiological mechanisms of diabetic kidney disease 5
Current Guidelines for Management
For patients with type 2 diabetes and CKD, SGLT2 inhibitors are recommended to reduce CKD progression and cardiovascular events in individuals with eGFR ≥20 mL/min/1.73 m² and urinary albumin ≥200 mg/g creatinine 2
SGLT2 inhibitors are also recommended for patients with eGFR ≥20 mL/min/1.73 m² and normal to moderately elevated urinary albumin (<200 mg/g creatinine) 2
ARBs are recommended for patients with diabetes, hypertension, and albuminuria, particularly those with macroalbuminuria 2
Maximum tolerated doses of ARBs should be used as clinical trials demonstrating efficacy used maximum doses, not suboptimal doses 2
Clinical Considerations for Combination Therapy
Monitor for potential side effects of combination therapy 1:
Do not discontinue ARB therapy for mild to moderate increases in serum creatinine (≤30%) in the absence of volume depletion 2
Avoid combining ACE inhibitors with ARBs as this combination has shown no benefits but increased adverse events (hyperkalemia and/or acute kidney injury) 2
Special Populations and Considerations
For patients with advanced CKD (eGFR <30 mL/min/1.73 m²), ARBs have demonstrated outcome benefits on both mortality and slowed CKD progression 2
SGLT2 inhibitors have shown efficacy in slowing CKD progression in patients with eGFR as low as 20 mL/min/1.73 m² 2
Multiple antihypertensive agents (typically 3 or more) are usually required to achieve target blood pressure in patients with diabetic kidney disease 2
Practical Implementation
- Start with maximum tolerated doses of ARBs 2
- Add SGLT2 inhibitor at the lowest dosage used in clinical trials 3
- Monitor for initial decline in eGFR upon SGLT2 inhibitor initiation, which is expected and not a reason to discontinue therapy 3
- Consider volume status when initiating combination therapy 3
- Target systolic blood pressure <130 mmHg in patients with diabetes and CKD 2
By combining these two medication classes that work through complementary mechanisms, patients with diabetic kidney disease can experience significant reductions in CKD progression and cardiovascular events beyond what either medication class can provide alone.