Can Jardiance Cause Urinary Frequency?
Yes, Jardiance (empagliflozin) directly causes increased urination including urinary frequency, pollakiuria (frequent urination), and nocturia as a predictable consequence of its mechanism of action as an SGLT2 inhibitor. 1
Mechanism and Incidence
Empagliflozin works by inhibiting glucose reabsorption in the renal proximal tubules, which creates an osmotic diuresis that leads to both increased urinary glucose excretion and increased urine volume 2. This is not a side effect but rather an expected pharmacologic effect of the drug.
According to FDA labeling data, increased urination (including polyuria, pollakiuria, and nocturia) occurred in 3.4% of patients on Jardiance 10 mg and 3.2% of patients on Jardiance 25 mg, compared to only 1.0% on placebo. 1 Specifically, nocturia was reported in 0.3% of patients on 10 mg, 0.8% on 25 mg, versus 0.4% on placebo 1.
In clinical studies, pollakiuria (frequent urination) was among the most frequently reported adverse events at 10.3% of patients 3. After a single dose, mean urine volume increased by 341 grams per day, though this effect diminished somewhat with continued dosing 4.
Clinical Characteristics
The urinary effects of empagliflozin follow a predictable pattern:
- Rapid onset: Urinary glucose excretion increases dramatically within 3 hours of the first dose (27-fold increase) 5
- Sustained effect: The increase in urinary glucose excretion is maintained over 28 days of treatment, ranging from 74-90 grams per day depending on dose 3
- Diuretic properties: Empagliflozin has both diuretic and natriuretic effects, promoting sodium excretion along with glucose 6, 5
- Transient natriuresis: After a single dose, sodium excretion increases by 45.3 mmol/day, though this effect diminishes with multiple doses 4
Volume Depletion Risk
The osmotic diuresis caused by Jardiance can lead to intravascular volume contraction and related adverse reactions. 1 Volume depletion-related events (including hypotension, dehydration, orthostatic hypotension, and syncope) occurred in 0.5% of patients on 10 mg and 0.3% on 25 mg versus 0.3% on placebo 1.
Patients at higher risk for volume depletion include:
- Elderly patients 1
- Patients with renal impairment 1
- Patients on diuretics or antihypertensive medications 7
- Patients with baseline volume depletion 1
Important Clinical Considerations
The urinary frequency from empagliflozin should not be confused with diabetic cystopathy or urinary tract infections, which can present with similar symptoms. 8 However, the persistent glucosuria creates a glucose-rich environment in the genitourinary tract, increasing the risk of urinary tract infections (reported in 9.3% on 10 mg and 7.6% on 25 mg versus 7.6% on placebo) 1.
Despite causing increased urination, empagliflozin does not cause the neurohormonal activation typically seen with traditional loop diuretics like furosemide. 5 This represents a favorable diuretic profile, as there was no evidence of potassium wasting or renal dysfunction associated with the natriuresis 5.
Management Approach
When patients report urinary frequency on Jardiance:
- Reassure patients that increased urination is an expected effect of the medication and typically diminishes somewhat after the initial dosing period 4
- Evaluate for volume depletion by checking orthostatic vital signs and assessing for symptoms of dehydration 1
- Rule out urinary tract infection with urinalysis and culture if dysuria or other infectious symptoms are present 8, 1
- Consider dose timing: Taking the medication earlier in the day may reduce nocturia impact
- Monitor renal function: Small increases in serum creatinine and decreases in eGFR can occur, particularly in patients with baseline renal impairment 1
Do not discontinue empagliflozin solely due to urinary frequency unless volume depletion or other complications develop, as the cardiovascular and renal protective benefits of the medication are substantial and independent of its glucose-lowering effects 2, 6.