Does Jardiance (Empagliflozin) Help with Proteinuria?
Yes, Jardiance (empagliflozin) reduces proteinuria and slows chronic kidney disease progression in patients with type 2 diabetes and diabetic kidney disease, particularly when albuminuria is present. 1
Evidence for Proteinuria Reduction
The most recent and highest quality guideline evidence demonstrates that SGLT2 inhibitors, including empagliflozin, provide significant renal protection:
Empagliflozin reduced the risk of incident or worsening nephropathy by 39% in the EMPA-REG OUTCOME trial, which included a composite of progression to macroalbuminuria (UACR >300 mg/g), doubling of serum creatinine, ESRD, or death from ESRD. 1
The risk of doubling serum creatinine accompanied by eGFR reduction was decreased by 44% with empagliflozin compared to placebo. 1
The baseline prevalence of albuminuria in EMPA-REG OUTCOME was 53%, and subgroup analyses suggested renal benefits were as great or greater for participants with CKD at baseline. 1
Current Guideline Recommendations
For patients with type 2 diabetes and diabetic kidney disease, use of an SGLT2 inhibitor (including empagliflozin) is recommended when eGFR >20 mL/min/1.73 m² and UACR >200 mg/g creatinine to reduce CKD progression and cardiovascular events. 1
This represents an important update from previous recommendations:
The eGFR threshold was lowered from >25 to >20 mL/min/1.73 m² based on subgroup analyses from DAPA-CKD and EMPEROR heart failure trials showing safety and efficacy at these lower eGFR levels. 1
The UACR threshold of >200 mg/g is based on DAPA-CKD enrollment criteria, though DECLARE-TIMI 58 suggested effectiveness even in participants with normal urinary albumin levels. 1
Mechanism of Proteinuria Reduction
Empagliflozin reduces proteinuria through multiple mechanisms beyond glycemic control:
Restoration of tubuloglomerular feedback and reduction in intraglomerular pressure by increasing afferent arteriolar tone, even in ambient normoglycemia. 1
Direct renal effects independent of glucose lowering, including reductions in systemic blood pressure, intraglomerular pressure, and albuminuria. 1
These hemodynamic changes slow GFR loss through mechanisms that appear independent of glycemia. 1
Clinical Considerations and Monitoring
Expected Initial Changes
An initial decline in eGFR of approximately 6.5% is expected within the first month of empagliflozin treatment, which is hemodynamic rather than representing structural kidney damage. 2
This initial eGFR decline is actually associated with greater proteinuria reduction—patients with larger initial eGFR declines tend to have better UPCR responses. 2
The eGFR decline is fully reversible upon discontinuation and represents beneficial intraglomerular pressure reduction. 3
Proteinuria Response Patterns
Proteinuria reduction is most significant in patients with baseline UPCR ≥0.5 g/gCr, with median UPCR decreasing significantly in this group but not in those with UPCR <0.5 g/gCr. 2
Patients whose UPCR decreased by >30% from baseline after 1 month (responders) had a greater initial decline in eGFR compared to non-responders. 2
Combination Therapy
While ACE inhibitors or ARBs remain the preferred first-line agents for blood pressure treatment in patients with diabetes, hypertension, eGFR <60 mL/min/1.73 m², and UACR ≥300 mg/g creatinine 1, empagliflozin should be added for additional renal protection:
Combination therapy with empagliflozin and ACE inhibitors (like lisinopril) provides additive benefits, reducing proteinuria, glomerular injury, and renal fibrosis more effectively than either agent alone. 4, 5
Preclinical models show over-additive reduction in proteinuria with low-dose combination therapy compared to respective monotherapies. 4
Important Caveats
The cardiovascular and renal benefits of empagliflozin likely outweigh concerns about modest elevations in hemoglobin that may occur with treatment. 6
Drug dosing may require modification when eGFR <60 mL/min/1.73 m², though empagliflozin can be safely used down to eGFR >20 mL/min/1.73 m². 1
Monitor for volume depletion, particularly in patients with nephrotic syndrome, by assessing for lightheadedness, orthostasis, and weakness. 7
The primary considerations when prescribing empagliflozin should remain its proven benefits in reducing cardiovascular events, heart failure hospitalizations, and slowing progression of diabetic kidney disease. 6