What are the management options for a patient with type 2 diabetes experiencing urinary urgency while taking Dapagliflozin (Forxiga)?

Management of Urinary Urgency in Patients Taking Dapagliflozin

Urinary urgency is a recognized dose-dependent adverse effect of dapagliflozin that occurs more frequently at the 10 mg dose (48% urgency, ~55% frequency) compared to 5 mg (20% urgency, ~25% frequency), and can be managed by dose reduction to 5 mg daily if cardiovascular/renal protection allows, or by discontinuation if symptoms are intolerable. 1

Understanding the Mechanism

• Dapagliflozin increases urinary glucose excretion by inhibiting SGLT2 in the proximal renal tubules, which leads to osmotic diuresis and increased urinary volume 2, 3
• The mechanism of action inherently causes glucosuria (approximately 70 grams of glucose excreted daily), which increases urine production and can trigger urgency symptoms 2
• This diuretic effect is most pronounced in the first few weeks of therapy and may improve with continued use as the body adapts 3

Clinical Assessment Algorithm

Determine if urgency is isolated or associated with infection:

• Check for dysuria, fever, or suprapubic pain—if present, obtain urinalysis and urine culture to rule out urinary tract infection 1, 4
• Women are at higher risk (76.2% of UTI cases) and require closer monitoring 4
• UTI incidence with dapagliflozin is approximately 5.3% overall, with most infections being mild to moderate 4, 5

Assess volume status and concurrent medications:

• Evaluate for signs of volume depletion (orthostatic hypotension, dizziness, dry mucous membranes), especially in elderly patients or those on concurrent diuretics 6, 2
• Consider reducing diuretic doses if volume depletion is contributing to urgency symptoms 6

Management Strategy Based on Indication

For patients on dapagliflozin primarily for glycemic control (eGFR ≥45 mL/min/1.73 m²):

• Reduce dose from 10 mg to 5 mg daily, which significantly decreases urgency symptoms (~48% to ~20%) while maintaining glycemic benefit 1, 6
• If urgency persists or is intolerable at 5 mg, discontinue dapagliflozin and switch to an alternative agent such as a GLP-1 receptor agonist (liraglutide, semaglutide) or DPP-4 inhibitor 6

For patients on dapagliflozin for cardiovascular/renal protection (heart failure, CKD with eGFR 25-75 mL/min/1.73 m²):

• The standard dose for cardiovascular and renal benefits is 10 mg daily, which cannot be reduced without potentially losing therapeutic benefit 7, 6
• If urgency is intolerable, you must weigh the significant mortality benefit (26% reduction in cardiovascular death or heart failure hospitalization, 39% reduction in kidney disease progression) against quality of life impact 7, 6
• Consider symptomatic management with behavioral modifications (timed voiding, pelvic floor exercises) before discontinuing the medication 1
• If discontinuation is necessary due to intolerable symptoms, ensure the patient remains on other guideline-directed medical therapy (ACE inhibitor/ARB, beta-blocker for heart failure) 7

Practical Management Steps

Immediate interventions:

• Rule out UTI with urinalysis if any signs of infection are present 4, 5
• Assess and correct volume depletion before attributing symptoms solely to dapagliflozin 6, 2
• Review timing of medication—taking dapagliflozin in the morning may reduce nighttime urgency 3

Dose adjustment protocol:

• For glycemic indication: reduce from 10 mg to 5 mg and reassess symptoms in 1-2 weeks 1, 6
• For cardiovascular/renal indication: maintain 10 mg if tolerable, as dose reduction is not recommended for these indications 7, 6

Patient education:

• Counsel that urgency symptoms typically improve after the first few weeks as the body adapts to increased urine output 3
• Advise adequate hydration to prevent volume depletion while managing urgency with timed voiding 6
• Educate on signs of UTI (dysuria, fever, suprapubic pain) and when to seek medical attention 4, 5

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin for cardiovascular/renal indications without considering the substantial mortality benefit—urgency is uncomfortable but rarely dangerous, whereas the conditions being treated are life-threatening 7, 6
• Do not assume urgency equals UTI—most urgency is due to osmotic diuresis, not infection; only 5.3% of patients develop actual UTIs 4, 5
• Do not reduce the dose below 10 mg for heart failure or CKD indications, as all cardiovascular and renal outcome trials used the fixed 10 mg dose 7, 6
• Do not overlook volume depletion from concurrent diuretics, which can exacerbate urgency symptoms and should be addressed first 6, 2

When to Discontinue Dapagliflozin

Absolute indications for discontinuation:

• Recurrent or severe UTIs requiring hospitalization 6
• Intolerable urgency that significantly impairs quality of life despite dose reduction (for glycemic indication only) 1
• Development of Fournier's gangrene (necrotizing fasciitis of the perineum), though extremely rare 6

Relative indications requiring careful consideration:

• Moderate urgency symptoms in patients on dapagliflozin for cardiovascular/renal protection—attempt symptomatic management first given the mortality benefit 7, 6