Dapagliflozin is Recommended for This Patient
This elderly male patient with type 2 diabetes, moderate CKD (GFR 46), hypertension, and cardiovascular risk factors is an excellent candidate for dapagliflozin, which should be initiated at 10 mg daily to reduce cardiovascular and renal disease progression. 1
Guideline-Based Rationale
Primary Indication: Renal and Cardiovascular Protection
SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) are specifically recommended for patients with eGFR 30 to <90 mL/min/1.73 m² to reduce renal endpoints and cardiovascular events. 1 This patient's GFR of 46 falls squarely within this therapeutic window.
The 2019 ESC guidelines explicitly state that treatment with an SGLT2 inhibitor is associated with lower risk of renal endpoints and is recommended if eGFR is 30 to <90 mL/min/1.73 m². 1
The DECLARE-TIMI 58 trial demonstrated that dapagliflozin reduced the composite of cardiovascular death or heart failure hospitalization (HR 0.83,95% CI 0.73-0.95) and achieved a 40% reduction in the composite of eGFR decline, renal replacement therapy, or renal death (HR 0.60,95% CI 0.47-0.77). 1
Addressing the Well-Controlled A1c (5.9%)
The primary indication here is NOT glycemic control but rather cardiovascular and renal protection. 1 The patient's excellent A1c of 5.9% should not dissuade initiation—in fact, it reduces hypoglycemia risk.
With such tight glycemic control, there is minimal risk of hypoglycemia when adding dapagliflozin, particularly if the patient is not on insulin or sulfonylureas. 2
Dosing and Initiation Strategy
Starting Dose
Initiate dapagliflozin 10 mg once daily regardless of the GFR of 46 mL/min/1.73 m². 2 The FDA label confirms that dapagliflozin was evaluated in 4304 patients with chronic kidney disease (eGFR 25-75 mL/min/1.73 m²) in the DAPA-CKD trial with consistent safety and efficacy. 2
No dose adjustment is required for eGFR ≥25 mL/min/1.73 m². 2
Pre-Initiation Assessment
Assess volume status before initiating dapagliflozin, particularly given the patient's age, hypertension, and potential diuretic use. 2 Elderly patients and those with impaired renal function (eGFR <60) are at increased risk for volume depletion. 2
Ensure the patient is not volume depleted or hypotensive before starting therapy. 2
Monitoring Plan
Renal Function Monitoring
Expect a small, transient decline in eGFR within the first 1-2 weeks of therapy (typically 2-4 mL/min/1.73 m²), which returns toward baseline by week 24. 3, 4 This is a hemodynamic effect, not renal injury.
In the DERIVE study of patients with CKD stage 3A (eGFR 45-59), dapagliflozin decreased eGFR by -2.49 mL/min/1.73 m² at week 24, but eGFR returned to baseline levels 3 weeks post-treatment. 4
Do not discontinue dapagliflozin if eGFR falls below 45 or even below 30 mL/min/1.73 m² during treatment, as cardiovascular and renal protective benefits persist. 2 Once initiated, patients in DAPA-CKD were not required to discontinue therapy even if eGFR fell below 25 mL/min/1.73 m² or dialysis was initiated. 2
Long-term, dapagliflozin slows the rate of eGFR decline compared to placebo (-1.09 vs -2.85 mL/min/1.73 m² per year in DAPA-HF). 5
Follow-Up Timeline
Recheck renal function, electrolytes, and volume status within 2-4 weeks of initiation. 6
Monitor blood pressure, as dapagliflozin may reduce systolic BP by approximately 3 mmHg. 4
Safety Considerations in This Patient
Volume Depletion and Hypotension Risk
Given the patient's age, hypertension treatment, and eGFR <60, he is at increased risk for volume depletion. 2 Monitor for signs of hypotension, particularly orthostatic symptoms.
The patient's diastolic dysfunction (grade 1) and vascular calcifications suggest underlying cardiovascular disease, but these are not contraindications—rather, they strengthen the indication for SGLT2 inhibitor therapy. 1
Genital Mycotic Infections
- Counsel the patient that genital mycotic infections occur in approximately 6% of patients on SGLT2 inhibitors versus 1% on placebo. 6, 2 These are typically mild and respond to standard antifungal therapy.
Urinary Tract Infections
- Monitor for signs and symptoms of urinary tract infections, including urosepsis and pyelonephritis, which have been reported with SGLT2 inhibitors. 2 Treat promptly if they occur.
Ketoacidosis Risk (Minimal in This Patient)
- The risk of diabetic ketoacidosis with dapagliflozin is very low in type 2 diabetes, particularly with well-controlled glucose (A1c 5.9%). 2 However, educate the patient to withhold dapagliflozin during acute illness, reduced oral intake, or before surgery. 2
Addressing Specific Comorbidities
Hypertension
Dapagliflozin will likely provide additional blood pressure reduction (approximately 3 mmHg systolic), which may be beneficial but requires monitoring to avoid excessive hypotension. 4
The 2024 ESC hypertension guidelines recommend individualized blood pressure management in elderly patients, with systolic BP targets of 120-129 mmHg if tolerated. 1
Diastolic Dysfunction and Vascular Calcifications
The presence of diastolic dysfunction (grade 1) and vascular calcifications indicates established cardiovascular disease, which is a Class I indication for SGLT2 inhibitor therapy. 1
DAPA-HF demonstrated that dapagliflozin reduced heart failure hospitalization by 27% (HR 0.73,95% CI 0.61-0.88) in patients with heart failure. 1
Common Pitfalls to Avoid
Do Not Withhold Due to Low A1c
- The most common error would be withholding dapagliflozin because the A1c is already well-controlled. 1 The primary benefit in this patient is cardiovascular and renal protection, not glycemic control.
Do Not Discontinue for Transient eGFR Decline
- Do not stop dapagliflozin if eGFR drops by 2-5 mL/min/1.73 m² in the first few weeks. 3, 4 This is expected and reversible.
Do Not Delay Initiation
- Given the patient's multiple cardiovascular risk factors (hypertension, diabetes, vascular calcifications, diastolic dysfunction), delaying SGLT2 inhibitor therapy represents a missed opportunity for proven cardiovascular and renal protection. 1
Patient Education
Instruct the patient to maintain adequate hydration, particularly during hot weather or illness. 2
Educate about signs of genital infections and urinary tract infections. 2
Advise temporary discontinuation during acute illness with reduced oral intake, fever, vomiting, or diarrhea. 2
Emphasize that this medication is primarily for heart and kidney protection, not just blood sugar control. 1