What serum creatinine and estimated glomerular filtration rate (eGFR) thresholds are required before starting dapagliflozin in a patient with type 2 diabetes, and how should renal function be monitored after initiation?

Renal Function Monitoring for Dapagliflozin

Check eGFR before starting dapagliflozin and ensure it is ≥25 mL/min/1.73 m² for cardiovascular/renal protection, or ≥45 mL/min/1.73 m² if the primary goal is glycemic control. 1

Pre-Initiation Assessment

Baseline Requirements:

• Measure eGFR and serum creatinine before initiating dapagliflozin to establish baseline renal function 1, 2
• For glycemic control: Do not initiate if eGFR <45 mL/min/1.73 m², as glucose-lowering efficacy is significantly reduced due to the drug's mechanism of action 1
• For cardiovascular/renal protection: Can initiate if eGFR ≥25 mL/min/1.73 m² regardless of diabetes status 1, 2
• Assess volume status before starting and correct any volume depletion, particularly in elderly patients (≥65 years) or those on concurrent diuretics 1

Post-Initiation Monitoring

Expected Initial eGFR Changes:

• Anticipate a transient eGFR decline of 3-5 mL/min/1.73 m² within the first 1-4 weeks after starting dapagliflozin—this is reversible and does not indicate kidney injury 1, 3
• Recheck eGFR and creatinine within 1-2 weeks after initiation to document this expected acute dip 1
• After week 2, eGFR stabilizes and dapagliflozin actually slows the chronic rate of eGFR decline compared to placebo by 0.95 mL/min/1.73 m² per year 3

Ongoing Monitoring Schedule:

• If eGFR 45-59 mL/min/1.73 m²: Recheck at least every 3-6 months 1
• If eGFR ≥60 mL/min/1.73 m²: Recheck annually 1
• If eGFR 25-44 mL/min/1.73 m²: Monitor more frequently (every 3 months) as these patients have more advanced CKD 1

Management Based on eGFR Changes

If eGFR Decreases >30% from Baseline:

• First assess for volume depletion (hypotension, orthostasis, reduced oral intake) 1
• If hypovolemia present: Reduce diuretic doses first before considering dapagliflozin adjustment 1
• Do not automatically discontinue dapagliflozin for eGFR decline alone, as patients with an initial eGFR reduction >10% at 2 weeks actually had better long-term renal outcomes (slower subsequent eGFR decline of -1.58 vs -2.44 mL/min/1.73 m²/year) 1

If eGFR Falls Below Initial Thresholds During Treatment:

• If eGFR falls below 45 mL/min/1.73 m²: Continue dapagliflozin 10 mg daily for cardiovascular/renal protection even though glycemic efficacy is lost 1, 2
• If eGFR falls below 25 mL/min/1.73 m²: May continue 10 mg daily until dialysis is initiated—do not discontinue 1, 2
• The cardiovascular and renal protective benefits persist at lower eGFR levels even when glucose-lowering effects are minimal 1

Critical Safety Monitoring

Situations Requiring Temporary Discontinuation:

• Hold dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea to prevent volume depletion and euglycemic diabetic ketoacidosis 1
• Withhold at least 3 days before major surgery or procedures requiring prolonged fasting 1
• Resume only after recovery and normal oral intake is re-established 1

Additional Monitoring Parameters:

• Volume status: Assess for signs of intravascular volume contraction, particularly in the first few weeks 1
• Genital mycotic infections: Occur in approximately 6% of patients on SGLT2 inhibitors vs 1% on placebo 1
• Euglycemic diabetic ketoacidosis: Monitor for malaise, nausea, vomiting even with normal blood glucose levels 1

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—the cardiovascular and renal benefits persist even when glycemic efficacy is lost 1
• Do not overreact to the initial transient eGFR dip in the first 1-4 weeks—this is expected and reversible 1, 3
• Do not reduce concurrent ACE inhibitors/ARBs when starting dapagliflozin unless there are specific clinical concerns 1
• Do not use serum creatinine alone to assess renal function—always calculate eGFR, and consider cystatin C-based eGFR if creatinine-based eGFR is 45-60 mL/min/1.73 m² with no other evidence of kidney damage 4