Do SGLT2 Inhibitors Increase Urination?
Yes, SGLT2 inhibitors definitively increase urination through an osmotic diuresis mechanism caused by blocking glucose reabsorption in the kidney, leading to increased urinary glucose excretion and subsequent increased urine volume. 1, 2
Mechanism of Action
SGLT2 inhibitors work by blocking the sodium-glucose cotransporter 2 protein in the proximal tubule of the nephron, which is responsible for approximately 90% of urinary glucose reabsorption. 1 This inhibition results in:
- Glucosuria (glucose in the urine) - the primary mechanism that forces glucose excretion rather than reabsorption 1
- Osmotic diuresis - the glucose in the urine pulls water with it, increasing urine volume 2
- Natriuretic effects - sodium excretion also increases, contributing to the diuretic effect 1
The mechanism is identical across all approved SGLT2 inhibitors (empagliflozin, dapagliflozin, and canagliflozin), as they are all highly selective for SGLT2 over SGLT1. 2
Clinical Significance of Increased Urination
Expected Effects
- Modest weight loss of 1.5-3.5 kg, partially attributable to fluid loss 3
- Systolic blood pressure reduction of 3-5 mm Hg due to the diuretic effect 1, 3
- Increased urination frequency is one of the most common adverse effects reported in clinical trials 3, 4
Populations Requiring Caution
Use SGLT2 inhibitors cautiously in older adults prone to orthostasis or urinary incontinence, as the increased urine volume may worsen pre-existing incontinence symptoms. 2 Specific concerns include:
- Volume depletion and hypotension risk is increased, particularly in frail older adults 2
- Orthostatic hypotension may occur due to the combined diuretic and natriuretic effects 2
Important Clinical Guidance
The American Heart Association recommends that patients should not discontinue SGLT2 inhibitors solely due to increased urination unless it significantly impairs quality of life, as the cardiovascular mortality reduction and kidney disease progression benefits substantially outweigh this tolerability issue. 2
Common Pitfalls to Avoid
- Do not confuse increased urination with urinary tract infections - large randomized controlled trials (EMPA-REG OUTCOME, CANVAS, CANVAS-R) demonstrated no difference in UTI rates compared to placebo despite the glucosuria 5
- Genital mycotic infections occur in approximately 6% of users versus 1% on placebo - these are typically mild and respond to brief antifungal courses without requiring drug discontinuation 5
- The increased urination is most pronounced when blood glucose is elevated - as blood glucose normalizes, glucosuria and the associated diuresis diminish 1
Patient Counseling Points
- Counsel patients to expect increased urination frequency, particularly during the first few weeks of therapy 3, 4
- Advise proper genital hygiene to prevent mycotic infections 5
- Monitor for signs of volume depletion, especially in patients taking concomitant diuretics or with baseline hypotension 2
- Reassure patients that increased urination does not indicate treatment failure but rather reflects the drug's intended mechanism of action 6, 7