Is it ok to increase dapagliflozin (Dapagliflozin) from 5 to 10 mg per day in a patient with Type 2 Diabetes Mellitus (T2DM) and Hypertension (HTN) with Impaired Renal Function (eGFR 35, creatinine clearance 47)?

Dapagliflozin Dose Increase in Elderly Patient with T2DM, HTN, and eGFR 35

No, do not increase dapagliflozin from 5 to 10 mg for glycemic control in this patient with eGFR 35 mL/min/1.73 m²; however, if the goal is cardiovascular or renal protection rather than glucose lowering, then yes, increase to 10 mg daily, as this is the evidence-based dose for cardiorenal benefits at this level of kidney function. 1, 2

Critical Decision Point: Indication Determines Dosing

The answer hinges entirely on why you're using dapagliflozin:

For Glycemic Control (NOT Recommended to Increase)

• Dapagliflozin is not recommended for glycemic control when eGFR <45 mL/min/1.73 m² because its glucose-lowering mechanism (inhibiting renal SGLT2) becomes ineffective as kidney function declines 1
• At eGFR 35, the drug's antihyperglycemic effects are significantly impaired, making dose escalation futile for glucose management 3
• The 5 mg dose already provides minimal glycemic benefit at this eGFR level 1, 2

For Cardiovascular/Renal Protection (RECOMMENDED to Increase)

• The evidence-based dose for cardiorenal protection is 10 mg daily, regardless of eGFR level down to 25 mL/min/1.73 m² 1, 2
• The DAPA-CKD trial demonstrated that dapagliflozin 10 mg reduced the composite outcome of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51-0.72) in patients with eGFR 25-75 mL/min/1.73 m² 4
• Cardiovascular death or heart failure hospitalization was reduced by 29% (HR 0.71,95% CI 0.55-0.92) at the 10 mg dose 4
• There is no evidence of graded dose-response for cardiovascular and renal benefits—the 10 mg dose tested in outcomes trials is what provides protection 1

Clinical Algorithm for This Patient

Step 1: Clarify the Primary Indication

• If the patient has established cardiovascular disease, heart failure, or CKD with albuminuria (UACR ≥200 mg/g), the primary indication should be cardiorenal protection, not glycemic control 1, 2
• At eGFR 35, glucose-lowering efficacy is minimal regardless of dose 1, 2

Step 2: If Cardiorenal Protection is the Goal

• Increase to dapagliflozin 10 mg once daily 1, 2
• This is safe and appropriate for eGFR ≥25 mL/min/1.73 m² 1, 2
• The creatinine clearance of 47 mL/min (which is higher than the eGFR of 35) does not change this recommendation—use eGFR for dosing decisions 1

Step 3: Safety Monitoring Before Dose Increase

• Assess volume status carefully before increasing the dose, as dapagliflozin has diuretic effects that may be enhanced in elderly patients with hypertension 1, 2
• Consider reducing concurrent diuretic doses if the patient is on loop or thiazide diuretics to prevent excessive volume depletion 1, 2
• Recheck eGFR within 1-2 weeks after dose increase—expect a transient dip of 3-5 mL/min/1.73 m² that typically stabilizes 2, 3

Step 4: Patient Education

• Counsel about genital mycotic infections (occurs in ~6% vs 1% placebo), which can be reduced with daily hygienic measures 2, 5
• Instruct to withhold dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea 2
• Educate about euglycemic diabetic ketoacidosis risk, though this is lower in patients not on insulin 1, 2

Common Pitfalls to Avoid

Pitfall #1: Discontinuing or Not Increasing Dose Because eGFR <45

• Many clinicians mistakenly stop or avoid increasing dapagliflozin when eGFR falls below 45 mL/min/1.73 m², thinking it's contraindicated 2
• The cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 1, 2
• The contraindication at eGFR <45 applies only to the glycemic control indication, not to cardiorenal protection 1

Pitfall #2: Using 5 mg for Cardiorenal Protection

• The 5 mg dose was not studied in cardiovascular or renal outcomes trials 1
• All cardiorenal benefits demonstrated in DAPA-CKD and DAPA-HF used the 10 mg dose 4
• Staying at 5 mg means the patient is not receiving the evidence-based protective dose 1, 2

Pitfall #3: Excessive Volume Depletion in Elderly Patients

• Elderly patients with hypertension on multiple antihypertensives are at higher risk for volume depletion when SGLT2 inhibitor dose is increased 1
• Proactively reduce diuretic doses before increasing dapagliflozin 2
• Monitor for orthostatic hypotension, dizziness, or acute kidney injury in the first 2 weeks 2

Alternative Glycemic Management at This eGFR

If glycemic control is inadequate at eGFR 35:

• GLP-1 receptor agonists (liraglutide, dulaglutide, semaglutide) require no dose adjustment and provide cardiovascular benefits at eGFR >30 mL/min/1.73 m² 1, 6
• DPP-4 inhibitors like linagliptin require no dose adjustment at any eGFR level 6
• Insulin remains effective regardless of kidney function and should be the primary glucose-lowering agent if needed 6
• Gliclazide can be used cautiously starting at 30 mg daily, as it's primarily hepatically metabolized 6

Bottom Line

Increase to dapagliflozin 10 mg daily if the goal is cardiovascular or renal protection (which it should be at eGFR 35), but do not increase the dose if the sole goal is glycemic control, as it will be ineffective. 1, 2, 4 The patient's eGFR of 35 mL/min/1.73 m² is well within the range where dapagliflozin 10 mg provides significant cardiorenal benefits, and the creatinine clearance of 47 mL/min does not contraindicate this increase. 1, 2