How to manage a patient on Dapagliflozin?

Management of a Patient on Dapagliflozin

Continue dapagliflozin for its proven cardiovascular and renal protective benefits, while monitoring for specific adverse effects and ensuring appropriate patient education about warning signs. 1

Continue Current Therapy

If the patient is already on dapagliflozin, continuation is strongly recommended for cardiovascular and kidney protection, regardless of the original indication. 1 The 2022 Mayo Clinic guidelines explicitly state that if already on dapagliflozin, it should be continued for kidney and cardiovascular benefits 1. This recommendation is supported by robust evidence from major trials showing:

• Cardiovascular benefits: Dapagliflozin reduces the composite of cardiovascular death or heart failure hospitalization by approximately 25%, with a 30% reduction in heart failure hospitalization specifically 1
• Renal protection: In the DAPA-CKD trial, dapagliflozin reduced the risk of kidney disease progression (≥50% sustained decline in eGFR, end-stage kidney disease, or renal/cardiovascular death) by 39% 2, 3
• Mortality benefit: Dapagliflozin reduces all-cause mortality by 17% and cardiovascular death by 18% 1

Monitor for Key Adverse Effects

Volume Depletion and Hypotension

• Assess volume status before each visit, particularly in elderly patients, those on loop diuretics, or those with eGFR <60 mL/min/1.73 m² 4
• Monitor for signs of symptomatic hypotension or acute transient changes in creatinine 4
• If volume depletion occurs, reduce diuretic doses first before considering dapagliflozin adjustment 2

Genital Mycotic Infections

• Educate patients about genital mycotic infections, which occur in 7.4-14.3% of patients (vs. 3.0% with placebo) 5
• Most infections are single episodes that respond to routine management 5
• Patients with a history of genital mycotic infections are at higher risk 4

Urinary Tract Infections

• Monitor for serious urinary tract infections including urosepsis and pyelonephritis, which can require hospitalization 4
• Urinary tract infections occur in 8.4-13.8% of patients (vs. 5.6% with placebo) 5
• Evaluate and treat promptly if symptoms develop 4

Ketoacidosis Risk

• Educate patients about diabetic ketoacidosis warning signs: nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath 4
• Blood glucose may be below typical DKA levels (<250 mg/dL) - this is "euglycemic DKA" 4
• Withhold dapagliflozin at least 3 days before scheduled surgery or procedures requiring prolonged fasting 1, 2
• Temporarily hold during acute illness with reduced oral intake, dehydration, or ketogenic diet 4

Fournier's Gangrene

• Assess immediately if patient presents with pain, tenderness, erythema, or swelling in the genital or perineal area with fever or malaise 4
• This is rare but life-threatening and requires urgent surgical intervention 4

Renal Function Monitoring

Expected eGFR Changes

• An initial eGFR decline of 3-5 mL/min/1.73 m² is expected within the first 1-4 weeks and is transient and reversible 1, 2
• This "eGFR dip" does not indicate harm; kidney function typically returns to baseline in following weeks 1
• Patients with an initial eGFR reduction >10% at 2 weeks actually had better long-term renal outcomes 2

Continuation Thresholds

• Continue dapagliflozin even if eGFR falls below 25 mL/min/1.73 m² in patients already on therapy 2, 4
• Do not initiate dapagliflozin if eGFR <25 mL/min/1.73 m² 2
• For glycemic control specifically, dapagliflozin is not recommended when eGFR <45 mL/min/1.73 m² as glucose-lowering efficacy is significantly reduced 2, 6
• However, cardiovascular and renal benefits persist at lower eGFR levels 2

Monitoring Schedule

• Check eGFR and creatinine within 1-2 weeks after initiation 2
• Assess renal function periodically thereafter 2
• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first 2

Medication Interactions

Insulin and Insulin Secretagogues

• Consider reducing insulin or sulfonylurea doses when used with dapagliflozin to minimize hypoglycemia risk 4
• Dapagliflozin increases hypoglycemia risk when combined with these agents 4

Diuretics

• Evaluate need for diuretic dose adjustment at initiation, but it is not usually necessary to stop or alter diuretic therapy 1
• Patients on loop diuretics are at increased risk for volume depletion 4

Patient Education Priorities

Provide specific counseling on:

• Sick day rules: Stop dapagliflozin during acute illness with dehydration, reduced oral intake, or diarrhea 1
• Ketoacidosis warning signs: Seek immediate medical attention for nausea, vomiting, abdominal pain, or shortness of breath even if blood glucose is normal 4
• Genital infection prevention: Maintain good hygiene; report severe or worsening infections 1
• Surgical planning: Inform all healthcare providers about dapagliflozin use; must be stopped ≥3 days before surgery 1
• Adequate hydration: Maintain fluid intake, especially during illness 1

Special Populations

Elderly Patients (≥65 years)

• Higher proportion experience hypotension 4
• Increased risk for volume depletion 4
• Monitor volume status and blood pressure more closely 4

Patients with Heart Failure

• Dapagliflozin provides substantial benefit with 25% reduction in cardiovascular death or heart failure hospitalization 1
• Benefits are consistent regardless of ejection fraction (HFrEF or HFpEF) 1, 4
• Absolute risk reductions are larger in heart failure patients 3

Patients with Chronic Kidney Disease

• Continue therapy for renal protection even as eGFR declines 2, 6
• Dapagliflozin slows eGFR decline rate and reduces risk of end-stage kidney disease by 44% 2
• Benefits are independent of diabetes status 3

When to Consider Discontinuation

Temporarily hold dapagliflozin if:

• Acute illness with dehydration or reduced oral intake 4
• ≥3 days before scheduled surgery or procedures requiring prolonged fasting 1, 2
• Suspected ketoacidosis (discontinue immediately and evaluate) 4
• Suspected Fournier's gangrene (discontinue immediately) 4

Resume when:

• Patient is clinically stable and has resumed oral intake 4
• Ketoacidosis has resolved (if that was the reason for holding) 4

Permanent discontinuation considerations:

• History of serious hypersensitivity reaction to dapagliflozin 4
• Recurrent severe ketoacidosis episodes 4
• Initiation of dialysis (though continuation may be considered if already on therapy) 6, 4