Does Jardiance Have a Diuretic Effect?
Yes, Jardiance (empagliflozin) definitively has both diuretic and natriuretic effects through its mechanism of action as an SGLT2 inhibitor. 1
Mechanism of Diuretic Action
SGLT2 inhibitors like empagliflozin cause diuresis through two primary mechanisms:
Osmotic diuresis from glucosuria: By blocking glucose reabsorption in the proximal tubule, empagliflozin induces urinary glucose excretion, which creates an osmotic effect that pulls water into the urine 1, 2
Natriuretic effect: Empagliflozin causes sodium excretion, which contributes significantly to the diuretic effect, particularly during initial treatment 1, 3
The diuretic effect is most pronounced when blood glucose is elevated, as more glucose is filtered and excreted; the effect diminishes as blood glucose normalizes 1
Clinical Manifestations of the Diuretic Effect
Patients experience measurable increases in urination, particularly in the initial treatment phase:
- Increased urination (polyuria, pollakiuria, nocturia) occurs more frequently with empagliflozin than placebo 4
- Nocturia specifically was reported in 0.8% of patients on empagliflozin 25 mg versus 0.4% on placebo 4
- The diuretic effect is typically transient, with urine volume increasing on Day 1 of treatment but returning toward baseline levels thereafter, despite sustained glucosuria 3, 5
Compensatory Mechanisms
The body activates several compensatory responses to the diuretic effect:
- Increased vasopressin secretion stimulates water reabsorption to maintain body fluid volume 5
- Increased plasma renin activity occurs as a compensatory mechanism for sodium retention 3
- Decreased plasma atrial natriuretic peptide (ANP) and NT-proBNP levels 3
- These mechanisms help stabilize body fluid volume despite ongoing diuresis 5
Clinical Implications and Monitoring
The diuretic effect has important clinical consequences that require monitoring:
Volume depletion risk: Empagliflozin causes osmotic diuresis that may lead to intravascular volume contraction, with adverse reactions related to volume depletion (hypotension, dehydration, orthostatic hypotension) reported in 0.3% of patients on empagliflozin 25 mg 4
Additive effects with loop diuretics: Patients should be advised that empagliflozin has potentially additive natriuretic effects when combined with loop diuretics 1
High-risk populations require careful monitoring: Elderly patients, those on concurrent diuretic therapy, patients with low blood pressure, those on low sodium diets, and patients with kidney problems are at higher risk for volume depletion 1, 4
Monitor for orthostatic symptoms: Patients should be advised to watch for signs of volume depletion such as orthostatic lightheadedness, dizziness, or feeling faint, especially when standing up 1, 4
Blood Pressure Reduction
The diuretic and natriuretic effects contribute to blood pressure lowering:
- Empagliflozin reduces systolic blood pressure by approximately 4 mm Hg and diastolic blood pressure by approximately 2 mm Hg 2
- This blood pressure reduction, along with weight loss, is one of the proposed mechanisms underlying the cardiovascular benefits of SGLT2 inhibitors 1
Common Pitfalls to Avoid
Do not discontinue or reduce diuretic therapy preemptively when initiating empagliflozin, as it is usually not necessary to alter concurrent diuretic therapy 1
Do not confuse the transient nature of increased urine volume with lack of drug effect, as glucosuria remains sustained even after urine volume normalizes 3, 5
Do not overlook thirst as a compensatory mechanism: Thirst and polydipsia were reported in 1.5-1.7% of patients on empagliflozin versus 0% on placebo, representing the body's attempt to maintain fluid balance 4