Can a patient with hemoglobin A1c of 9% be started on empagliflozin (Jardiance) at 25 mg once daily?

Starting Empagliflozin (Jardiance) at 25 mg in a Patient with HbA1c 9%

You should start empagliflozin at 10 mg once daily, not 25 mg, because the 10 mg dose provides identical cardiovascular and renal protection while minimizing adverse effects, and you can increase to 25 mg after 4–12 weeks only if additional glucose lowering is needed and eGFR remains ≥45 mL/min/1.73 m².

Initial Dosing Strategy

• The FDA-approved starting dose of empagliflozin is 10 mg once daily, taken in the morning with or without food 1.

• Both the 10 mg and 25 mg doses produce identical reductions in cardiovascular death, heart failure hospitalization, and major adverse cardiovascular events, demonstrating no dose-response relationship for cardiorenal protection 2, 3.

• The American College of Cardiology explicitly recommends initiating empagliflozin at the lowest approved dose (10 mg daily) for cardiovascular risk reduction, stating that higher doses do not confer additional CV benefit 2.

When to Consider Dose Escalation

• After starting at 10 mg daily, you may increase to 25 mg once daily after 4–12 weeks if:

  • HbA1c remains above target despite the 10 mg dose 3
  • eGFR is ≥45 mL/min/1.73 m² 3, 1
  • The primary goal is additional glucose lowering, not cardiovascular or renal protection 2, 3

• Do not increase the dose from 10 mg to 25 mg for cardiovascular or renal protection, as the higher dose offers no additional benefit and raises adverse-event risk 2, 3.

Evidence Supporting 10 mg as the Starting Dose

• In the EMPA-REG OUTCOME trial, empagliflozin 10 mg and 25 mg produced identical hazard ratios for:

  • 3-point MACE: 0.86 (0.74–0.99) 4
  • Cardiovascular death: 0.62 (0.49–0.77) 4
  • Heart failure hospitalization: 0.65 (0.50–0.85) 4
  • All-cause mortality: 0.68 (0.57–0.82) 4

• The 10 mg dose reduced incident or worsening nephropathy by 39% (HR 0.61,95% CI 0.53–0.70), with no additional renal benefit from the 25 mg dose 5.

Glycemic Efficacy at Different Doses

• At 12 weeks, empagliflozin produces dose-dependent HbA1c reductions:

  • 10 mg: approximately -0.5% 6
  • 25 mg: approximately -0.6% 6

• For a patient with HbA1c 9%, starting at 10 mg will reduce HbA1c by roughly 0.5%, bringing it to approximately 8.5% 6, 7.

• If this reduction is insufficient after 4–12 weeks and eGFR remains ≥45 mL/min/1.73 m², escalating to 25 mg may provide an additional 0.1–0.2% HbA1c reduction 7.

Safety Considerations Favoring 10 mg Start

• The 25 mg dose is associated with a higher rate of genital mycotic infections (≈6% vs ≈4% with 10 mg) 2, 3.

• Volume depletion and urinary tract infections occur more frequently with the 25 mg dose, particularly in elderly patients or those with reduced renal function 2, 3.

• Starting at 10 mg allows you to assess tolerability before considering dose escalation 3.

Pre-Initiation Assessment

Before starting empagliflozin at any dose, you must:

• Check eGFR: Do not initiate if eGFR is <45 mL/min/1.73 m² 1.

• Assess volume status and correct any depletion; consider reducing concurrent diuretic doses, especially in elderly patients 3.

• Exclude contraindications: pregnancy, breastfeeding, type 1 diabetes, or dialysis 3.

Concomitant Medication Adjustments

• If the patient is on insulin or a sulfonylurea and baseline HbA1c is <8.5%, reduce the dose of insulin/sulfonylurea by ≈20% to lower hypoglycemia risk 3.

• Discontinue sulfonylureas entirely when HbA1c is already <8.5%, as the combination adds hypoglycemia risk without extra cardiovascular benefit 3.

• Continue ACE inhibitors or ARBs unchanged when starting empagliflozin 3.

Monitoring After Initiation

• Re-measure eGFR 1–2 weeks after starting empagliflozin; an expected hemodynamic dip of 3–5 mL/min/1.73 m² should not prompt discontinuation 2, 3.

• Monitor blood glucose closely for the first 2–4 weeks, especially if insulin or sulfonylureas are still being used 3.

• Re-assess HbA1c at 4–12 weeks to determine whether dose escalation to 25 mg is warranted 3.

Common Pitfalls to Avoid

• Do not start at 25 mg simply because HbA1c is high; the 10 mg dose provides full cardiorenal protection and substantial glucose lowering 2, 3.

• Do not increase to 25 mg for cardiovascular or renal protection; the higher dose offers no additional benefit for these outcomes 2, 3.

• Do not discontinue empagliflozin if eGFR falls below 45 mL/min/1.73 m² after initiation; cardiovascular and renal benefits persist even when glucose-lowering efficacy is lost 2, 3.

• Do not stop the drug in response to the expected early eGFR dip; this change is hemodynamic, reversible, and protective 2, 3.