What is the recommended starting dose of dapagliflozin (SGLT2 inhibitor) for a patient with impaired renal function, specifically an estimated Glomerular Filtration Rate (eGFR) of 38?

Dapagliflozin Dosing in Patients with eGFR 38 mL/min/1.73 m²

The recommended starting dose of dapagliflozin for a patient with an eGFR of 38 mL/min/1.73 m² is 10 mg once daily. 1

Dosing Rationale Based on Renal Function

According to the 2022 American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) consensus report, dapagliflozin can be initiated at 10 mg daily in patients with eGFR between 30-44 mL/min/1.73 m² (Stage 3b CKD). 1

The dosing recommendations are clearly outlined:

• eGFR 30-44 mL/min/1.73 m² (Stage 3b): 10 mg daily
• eGFR 25-29 mL/min/1.73 m² (Stage 4): Initiation not recommended
• eGFR <25 mL/min/1.73 m²: Initiation not recommended

Continuation of Therapy with Declining Renal Function

An important clinical consideration is that once dapagliflozin is initiated, it can be continued even if eGFR subsequently falls below the initiation threshold. The medication can be continued for kidney and cardiovascular benefits until dialysis is required. 1

Efficacy Considerations

It's important to note that while the glucose-lowering efficacy of dapagliflozin decreases as eGFR declines, the kidney and cardiovascular benefits are preserved even at lower eGFR levels. 1 This makes dapagliflozin particularly valuable in this patient population for its cardiorenal protective effects beyond glycemic control.

Monitoring Recommendations

When initiating dapagliflozin in a patient with eGFR 38 mL/min/1.73 m²:

1. Initial eGFR response: Expect a small, transient decline in eGFR after initiation, which is generally reversible and does not require discontinuation. 2

2. Volume status: Monitor for signs of volume depletion, especially if the patient is on diuretics. Consider proactive dose reduction of diuretics in high-risk patients. 1

3. Ketoacidosis risk: Educate the patient about signs/symptoms of ketoacidosis and implement a sick day protocol. If the patient is on insulin, maintain at least a low dose to prevent ketosis. 1

4. Genital mycotic infections: Counsel on genital hygiene to reduce the risk of genital mycotic infections, which occur in approximately 6% of patients on SGLT2 inhibitors compared to 1% on placebo. 1

Clinical Evidence Supporting This Recommendation

The DERIVE study specifically evaluated dapagliflozin in patients with T2D and moderate renal impairment (CKD stage 3A, eGFR 45-59 mL/min/1.73 m²) and found that dapagliflozin 10 mg was effective and well-tolerated. 3

Additionally, the DAPA-CKD trial demonstrated significant benefits of dapagliflozin in patients with CKD (eGFR 25-75 mL/min/1.73 m²), showing a 39% reduction in the risk of a composite of sustained decline in eGFR, end-stage kidney disease, or death from renal or cardiovascular causes. 4

Common Pitfalls to Avoid

1. Discontinuing too early: Don't discontinue dapagliflozin if there's an initial small decline in eGFR after starting therapy, as this is expected and usually transient. 2

2. Missing cardiovascular benefits: Don't focus solely on glycemic control when evaluating efficacy in patients with reduced renal function. The cardiovascular and renal benefits persist even when glucose-lowering effects diminish. 1

3. Inadequate patient education: Failure to educate patients about sick day management and when to temporarily hold the medication can increase the risk of adverse events like ketoacidosis. 1

4. Overlooking drug interactions: Be cautious with concomitant diuretics, as the combination may increase the risk of volume depletion. 1