Can Dapagliflozin Be Started in This Patient?
Yes, dapagliflozin 10 mg once daily should be initiated in this patient for cardiovascular and renal protection, despite the creatinine clearance of 21 mL/min, because the patient has just recovered from acute pulmonary congestion and the drug provides robust mortality and heart failure benefits at this level of renal function. 1
Evidence Supporting Initiation at eGFR ≥20 mL/min
The 2024 American Diabetes Association guidelines explicitly recommend initiating dapagliflozin when eGFR is ≥20 mL/min/1.73 m² for cardiovascular and renal protection, representing a significant update from previous thresholds. 1
The DAPA-CKD trial enrolled patients with eGFR as low as 25 mL/min/1.73 m² and demonstrated a 39% reduction in the composite outcome of sustained eGFR decline, end-stage kidney disease, or cardiovascular/renal death (HR 0.61,95% CI 0.51–0.72). 2
Most importantly for this patient with recent pulmonary congestion, dapagliflozin reduced cardiovascular death or heart failure hospitalization by 29% (HR 0.71,95% CI 0.55–0.92) and all-cause mortality by 31% (HR 0.69,95% CI 0.53–0.88). 2, 1
The EMPA-KIDNEY trial (a sister SGLT2 inhibitor study) enrolled patients with eGFR as low as 20 mL/min/1.73 m² and showed consistent cardiovascular and renal benefits, supporting the safety and efficacy of this drug class at very low eGFR levels. 2
Critical Distinction: Glycemic Control vs. Cardiorenal Protection
Do not initiate dapagliflozin for glycemic control at this eGFR level—the glucose-lowering effect is minimal because the drug's mechanism (blocking renal glucose reabsorption) requires adequate glomerular filtration. 1
Initiate dapagliflozin specifically for cardiovascular and renal protection, where the benefits are preserved even at eGFR 20–25 mL/min/1.73 m². 1
The fixed dose is 10 mg once daily for cardiovascular/renal indications regardless of renal function, with no titration required. 1
Pre-Initiation Safety Assessment
Volume Status Correction (Critical in This Patient)
Before starting dapagliflozin, ensure the patient is euvolemic—the recent acute pulmonary congestion suggests prior volume overload, but you must confirm the patient is now clinically dry without residual congestion. 1
If the patient is on loop diuretics (likely given the recent pulmonary edema), consider a modest diuretic dose reduction when starting dapagliflozin to prevent excessive volume depletion. 1
Dapagliflozin causes osmotic diuresis (approximately 70 grams of glucose excreted daily, resulting in increased urinary volume), which can lead to intravascular volume contraction, particularly in elderly patients. 3, 4
Age-Related Considerations
Patients in their late 80s face increased risks of hypotension and volume depletion with SGLT2 inhibitors, but these risks do not contraindicate use—they require heightened vigilance. 1
In the pooled analysis of dapagliflozin trials, patients ≥75 years had more adverse events than younger patients (80.4% vs. 73.1% with dapagliflozin), but serious adverse events were similar (19.6% vs. 18.2% compared to placebo). 4
Volume reduction adverse events were uncommon but slightly higher in patients ≥75 years (3.1% with dapagliflozin vs. 2.6% with placebo). 4
Expected Renal Function Changes
An acute, reversible eGFR decline of 2–5 mL/min/1.73 m² is expected within the first 2–4 weeks of dapagliflozin initiation—this hemodynamic dip reflects reduced intraglomerular pressure and should not prompt discontinuation. 1, 5
Check eGFR and creatinine within 1–2 weeks after initiation to document this expected change and rule out true tubular injury (which would require urine microscopy if suspected). 1, 5
After the initial dip, eGFR typically stabilizes and the long-term trajectory shows slower decline compared to placebo. 2, 1
Dosing and Administration
Start dapagliflozin 10 mg orally once daily—this is the fixed dose for all cardiovascular and renal indications, with no dose adjustment needed for renal function. 1
Dapagliflozin can be taken with or without food (high-fat meals decrease Cmax by 50% but do not alter AUC, which is not clinically meaningful). 3
The plasma half-life is approximately 12.9 hours, allowing once-daily dosing. 3
Medication Adjustments
Insulin or Sulfonylurea
- If the patient is on insulin or a sulfonylurea, reduce the dose of these agents when starting dapagliflozin to mitigate hypoglycemia risk, and monitor glucose closely for the first 2–4 weeks. 1
ACE Inhibitors or ARBs
- Continue ACE inhibitors or ARBs without dose adjustment when dapagliflozin is started—over 99% of DAPA-CKD participants were on renin-angiotensin system blockers, and the combination showed additive renal protection. 2, 1
Diuretics
- If the patient is on loop or thiazide diuretics (likely given the recent pulmonary congestion), consider a modest diuretic dose reduction at initiation to avoid excessive volume depletion. 1
Safety Precautions and Patient Education
Sick Day Rules (Critical)
Temporarily withhold dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea to prevent volume depletion and euglycemic diabetic ketoacidosis. 1, 6
Stop dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 1, 6
If dapagliflozin must be held temporarily and the patient is on insulin, maintain a low-dose insulin regimen to prevent hyperglycemia and ketoacidosis. 1, 6
Euglycemic Diabetic Ketoacidosis
Warn the patient that euglycemic DKA can occur even with normal blood glucose levels when taking dapagliflozin, and advise immediate medical evaluation for malaise, nausea, vomiting, or abdominal pain. 1, 6
DKA risk is increased during acute illness, reduced insulin doses, or continued SGLT2 inhibitor use during illness. 6
Genital Mycotic Infections
Counsel the patient that genital mycotic infections occur in approximately 6% of treated individuals versus 1% with placebo—emphasize daily hygiene to reduce this risk. 1
No serious genital infection adverse events were reported in the pooled analysis of older patients. 4
Urinary Tract Infections
- Urinary tract infection frequency was similar between dapagliflozin and placebo in older patients (8.2% vs. 9.1% in patients ≥75 years), with rare serious events. 4
Monitoring Plan
Check eGFR and creatinine within 1–2 weeks after initiation to document the expected hemodynamic dip. 1
Assess volume status closely in the first few weeks, particularly given the patient's age and recent pulmonary congestion. 1
Monitor blood pressure for hypotension, especially if the patient is on concurrent diuretics or antihypertensives. 4
Recheck eGFR at least every 3–6 months if eGFR is 20–44 mL/min/1.73 m². 1
Common Pitfalls to Avoid
Do not discontinue dapagliflozin when eGFR falls below 25 mL/min/1.73 m²—cardiovascular and renal benefits persist, and the drug can be continued until dialysis is initiated. 1
Do not stop the drug because of the expected initial eGFR dip in the first 2–4 weeks—this is a hemodynamic effect, not tubular injury. 1, 5
Do not reduce the dose below 10 mg for cardiovascular or renal indications, even if glycemic efficacy wanes at lower eGFR. 1
Do not withhold ACE inhibitors or ARBs when starting dapagliflozin—the combination provides additive renal protection. 1
Renal Adverse Events in Older Patients
Renal adverse events were more common with dapagliflozin than placebo and increased with age (29.9% vs. 20.8% in patients ≥75 years), but most were non-serious small transient increases in serum creatinine. 4
No events of acute tubular necrosis were reported in the pooled analysis. 7