Glucosuria and Empagliflozin Therapy

Mechanism of Action and Effects

Empagliflozin has both diuretic and natriuretic effects, promoting sodium excretion along with glucose, contributing to blood pressure reduction of approximately 4 mmHg systolic and 2 mmHg diastolic, as noted by Praxis Medical Insights 1

The persistent glucosuria creates a glucose-rich environment in the genitourinary tract, increasing the risk of mycotic genital infections, particularly in women, with genital mycotic infections occurring in approximately 6% of patients on SGLT2 inhibitors versus 1% on placebo, according to Kidney International 2
Empagliflozin should be continued even when eGFR falls below initiation thresholds (≥20 mL/min/1.73 m²) for its cardiovascular and renal protective benefits, despite diminished glucose-lowering effects, as recommended by Kidney International and the American College of Cardiology 2, 3

Empagliflozin works by inhibiting glucose reabsorption in the renal proximal tubules, creating an osmotic diuresis that leads to increased urinary glucose excretion and urine volume, as reported by the American Diabetes Association 4, 5

The American College of Cardiology recommends considering the cardiovascular and renal protective benefits of empagliflozin, which are substantial and independent of its glucose-lowering effects, when managing patients with urinary frequency 6, 7

The American Diabetes Association recommends that empagliflozin be continued for cardiovascular and kidney benefits even when eGFR falls below 45 mL/min/1.73 m² until dialysis or transplantation, despite minimal glucose-lowering effects at these levels 8
Empagliflozin reduces the risk of incident or worsening nephropathy by 39% and the risk of doubling of serum creatinine accompanied by eGFR reduction by 44% in cardiovascular outcomes trials 9

The American Diabetes Association guidelines suggest that empagliflozin can be initiated if eGFR is above 20 mL/min/1.73 m² 10
Empagliflozin should be continued for cardiovascular and kidney benefit until dialysis or transplantation, even when eGFR falls below 45 mL/min/1.73 m², with minimal glucose-lowering efficacy at these levels 8, 11

The American Diabetes Association recommends against discontinuing empagliflozin solely because eGFR falls below 45 mL/min/1.73 m² in patients already taking it, as the cardiovascular and renal benefits persist even when glucose-lowering effects diminish 8, 10