In a 67‑year‑old patient with type 2 diabetes, hypertension and an HbA1c of 7.4% who is on metformin, should empagliflozin be added to the regimen or replace metformin?

Empagliflozin Should Be Added to Metformin, Not Used as Replacement

For this 67-year-old patient with type 2 diabetes (HbA1c 7.4%) and hypertension on metformin, empagliflozin should be added to the existing metformin regimen rather than replacing it. This combination approach provides superior cardiovascular and renal protection while maintaining the proven glycemic benefits of metformin 1.

Rationale for Combination Therapy

Guideline-Directed Approach

• The 2025 ADA Standards of Care explicitly recommend that SGLT2 inhibitors like empagliflozin be added to metformin (not as replacement) for patients with type 2 diabetes and cardiovascular risk factors, independent of HbA1c level 1.

• For patients with hypertension (a cardiovascular risk factor), an SGLT2 inhibitor with demonstrated cardiovascular benefit is recommended as part of the glucose-lowering regimen "with or without metformin use" 1. This phrasing indicates empagliflozin is added alongside metformin, not instead of it.

• The European Society of Cardiology guidelines specifically recommend the combination of metformin and SGLT2 inhibitors like empagliflozin for optimal management of type 2 diabetes in patients with or at risk for cardiovascular disease 2.

Why Continue Metformin

• Metformin remains the foundational first-line therapy for type 2 diabetes due to its well-documented efficacy, safety profile, low cost, and potential cardiovascular benefits 1.

• All major cardiovascular outcomes trials of SGLT2 inhibitors (including empagliflozin) were conducted with 70-99% of participants already taking metformin at baseline 1. The proven benefits of empagliflozin were demonstrated on top of metformin therapy, not as a replacement.

• There is no evidence supporting discontinuation of effective metformin therapy when adding empagliflozin 1.

Practical Implementation Algorithm

Step 1: Verify Metformin Can Be Continued

• Check eGFR: Metformin should be continued if eGFR ≥45 mL/min/1.73 m² at full dose 1.
• If eGFR is 30-44 mL/min/1.73 m², reduce metformin to maximum 1000 mg daily 2.
• If eGFR <30 mL/min/1.73 m², metformin must be discontinued 1.

Step 2: Add Empagliflozin to Existing Metformin

• Start empagliflozin 10 mg once daily as add-on to current metformin dose 1.
• If additional glycemic control is needed after 12 weeks, increase to empagliflozin 25 mg once daily 1.
• For cardiovascular/renal protection, empagliflozin can be initiated if eGFR ≥25 mL/min/1.73 m² (or ≥20 mL/min/1.73 m² per 2025 ADA guidelines) 1, 3.

Step 3: Monitor and Adjust

• Recheck HbA1c in 3 months 1.
• Monitor eGFR within 1-2 weeks after starting empagliflozin, then every 3-6 months 3.
• Assess for volume depletion, especially if patient is on concurrent diuretics for hypertension 3.

Evidence Supporting Combination Therapy

Cardiovascular and Renal Benefits

• Empagliflozin added to metformin reduces cardiovascular death by 38% and the composite outcome of MI, stroke, or cardiovascular death by 14% in patients with established cardiovascular disease 1.

• The combination provides renal protection with 39-44% reduction in kidney disease progression 3.

• These benefits are independent of baseline HbA1c and occur even when glycemic control is already adequate 1.

Glycemic Efficacy

• When empagliflozin is added to metformin, HbA1c reductions of 0.6-0.8% are consistently achieved 4, 5, 6.

• The combination of metformin plus empagliflozin is superior to metformin plus sulfonylurea for long-term glycemic durability and has significantly lower hypoglycemia risk 5.

• In patients already on metformin plus sulfonylurea, adding empagliflozin reduced HbA1c by an additional 0.77-0.82% 7.

Critical Safety Considerations

Volume Status Management

• Assess volume status before starting empagliflozin, particularly in elderly patients or those on diuretics for hypertension 3.
• Consider reducing diuretic doses when initiating empagliflozin to prevent excessive volume depletion 3, 2.

Sick Day Rules

• Educate patient to temporarily hold empagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea 3.
• Continue metformin during minor illness unless contraindicated 2.
• Withhold empagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting 3.

Monitoring for Adverse Effects

• Monitor for genital mycotic infections (occur in ~6% of patients on SGLT2 inhibitors) 3, 2.
• Watch for urinary tract infections, particularly in women 7.
• Be vigilant for euglycemic diabetic ketoacidosis, though rare 3.

Common Pitfall to Avoid

Do not discontinue metformin when adding empagliflozin unless there is a specific contraindication (such as eGFR <30 mL/min/1.73 m²) 1, 2. The cardiovascular and renal benefits of empagliflozin were proven in patients already taking metformin, and stopping metformin removes a proven, cost-effective therapy without evidence of benefit 1.