In a 79‑year‑old patient with type 2 diabetes, hemoglobin A1c 6.4 %, eGFR approximately 44 mL/min/1.73 m², currently taking metformin 500 mg daily and empagliflozin (Jardiance) 10 mg daily, should the empagliflozin dose be increased to 25 mg?

Should Empagliflozin (Jardiance) Be Increased from 10 mg to 25 mg?

No, do not increase empagliflozin from 10 mg to 25 mg in this 79-year-old patient with eGFR 44 mL/min/1.73 m² and HbA1c 6.4%. The 10 mg dose provides full cardiovascular and renal protection, and dose escalation offers no additional mortality or cardiorenal benefit while potentially increasing adverse effects 1, 2.

Evidence-Based Rationale

Cardiovascular and Renal Protection Is Dose-Independent

• The EMPA-REG OUTCOME trial demonstrated that empagliflozin 10 mg and 25 mg produced identical cardiovascular benefits, with no graded dose-response relationship for major adverse cardiovascular events, cardiovascular death, or heart failure hospitalization 1.

• The American College of Cardiology explicitly states that empagliflozin should be initiated at the lowest available dose (10 mg) for cardiovascular risk reduction, with no further up-titration needed for CV protection 1.

• All cardiovascular and renal outcome trials used fixed doses without titration, confirming that 10 mg delivers the full therapeutic benefit for mortality reduction 1.

Glycemic Control Is Already Optimal

• The patient's HbA1c of 6.4% is already at or below the recommended target for a 79-year-old with CKD, making additional glucose lowering unnecessary and potentially harmful due to hypoglycemia risk 1.

• At eGFR 44 mL/min/1.73 m², empagliflozin's glucose-lowering efficacy is markedly reduced regardless of dose, because the drug's mechanism (inhibiting renal glucose reabsorption) becomes less effective as kidney function declines 1, 2.

• Increasing to 25 mg would provide minimal additional glycemic benefit (perhaps 0.1–0.2% HbA1c reduction) while exposing the patient to higher rates of genital mycotic infections and volume depletion 3, 4.

Renal Function Considerations

• The FDA label specifies that empagliflozin dosing modifications are based on glycemic efficacy, not safety concerns, and that cardiovascular benefits persist down to eGFR 30 mL/min/1.73 m² at the 10 mg dose 1, 2.

• For patients with eGFR <45 mL/min/1.73 m², the 10 mg dose remains appropriate for cardiovascular and renal protection, but dose escalation for glycemic control is not recommended because glucose-lowering efficacy is lost 1, 2.

• The patient's eGFR of 44 mL/min/1.73 m² places him just below the threshold where dose increases for glycemic control would be considered, and his HbA1c does not justify such an increase 1, 2.

Safety Profile at Higher Doses

• Genital mycotic infections occur more frequently with 25 mg than 10 mg (approximately 6% vs. 4% in clinical trials), which is particularly relevant in elderly patients 3, 4.

• Volume depletion risk increases with higher doses, and this 79-year-old patient is already at elevated risk due to age and reduced eGFR 1, 2.

• The 25 mg dose provides no additional cardiovascular or renal protection compared to 10 mg, making the increased adverse-event risk unjustifiable 1.

Clinical Decision Algorithm

1. Confirm that the primary indication for empagliflozin is cardiovascular/renal protection (not glycemic control) given the patient's age, CKD, and optimal HbA1c 1.

2. Maintain empagliflozin 10 mg once daily as the fixed dose for cardiorenal protection 1, 2.

3. Do not increase to 25 mg because:

   • HbA1c 6.4% requires no additional glucose lowering 1
   • eGFR 44 mL/min/1.73 m² limits glucose-lowering efficacy of any dose 1, 2
   • Cardiovascular and renal benefits are identical between 10 mg and 25 mg 1
   • Higher dose increases adverse-event risk without added benefit 3, 4

4. Continue metformin 500 mg daily (already appropriately reduced for eGFR 44 mL/min/1.73 m²) 1.

5. Monitor eGFR every 3–6 months and continue empagliflozin 10 mg even if eGFR falls below 45 mL/min/1.73 m², as cardiorenal benefits persist 1, 2.

Common Pitfalls to Avoid

• Do not increase empagliflozin dose based on HbA1c alone when the patient is already at target and has reduced eGFR 1.

• Do not assume that higher doses provide greater cardiovascular or renal protection; the evidence shows no dose-response relationship for these outcomes 1.

• Do not discontinue empagliflozin if eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist at lower eGFR levels 1, 2.

• Do not overlook the increased adverse-event burden (genital infections, volume depletion) associated with 25 mg in elderly patients with CKD 3, 4.