My type 2 diabetes patient’s hemoglobin A1c rose from 7.4% to 8.3% after increasing empagliflozin (Jardiance) to 25 mg; what should be done?

Immediate Treatment Intensification Required

Your patient's A1C rising from 7.4% to 8.3% despite increasing empagliflozin to 25 mg indicates treatment failure requiring immediate addition of a GLP-1 receptor agonist or basal insulin. 1

Why Empagliflozin Alone Is Insufficient

• Empagliflozin 25 mg provides an average A1C reduction of only 0.6–0.8% when added to existing therapy, which is clearly inadequate for this patient whose A1C has increased rather than decreased 1, 2
• The dose escalation from 10 mg to 25 mg empagliflozin typically yields an additional 0.2–0.3% A1C reduction at most 3, 4, far short of the 1.3% reduction needed to reach target
• Empagliflozin's primary value lies in cardiovascular and renal protection, not aggressive glucose lowering 2, 1

Recommended Treatment Algorithm

Step 1: Add a GLP-1 Receptor Agonist (Preferred Option)

• GLP-1 receptor agonists provide 0.6–0.8% additional A1C reduction when added to SGLT2 inhibitors and offer proven cardiovascular mortality benefit 1
• Start semaglutide 0.25 mg subcutaneously weekly, increase to 0.5 mg after 4 weeks, then to 1.0 mg if needed 1
• Alternative: liraglutide 0.6 mg daily, increase to 1.2 mg after 1 week, then to 1.8 mg 1
• This combination maximizes cardiorenal protection while achieving glycemic control without significant hypoglycemia risk 1

Step 2: If GLP-1 RA Is Contraindicated or Not Tolerated, Initiate Basal Insulin

• Start basal insulin at 10 units once daily at bedtime OR 0.1–0.2 units/kg body weight 1
• Titrate by 2–4 units every 3 days until fasting glucose reaches 80–130 mg/dL 1
• Continue empagliflozin 25 mg for cardiovascular/renal protection even when adding insulin 1

Step 3: Ensure Metformin Is Optimized

• If the patient is not already on metformin, start it immediately at 500 mg once or twice daily with meals, titrating to 2000 mg daily (1000 mg twice daily) 1
• Metformin must remain foundational therapy throughout intensification unless eGFR <30 mL/min/1.73 m² 1
• Never discontinue metformin when adding other agents—it reduces cardiovascular mortality and lowers insulin requirements 1

Expected Outcomes with Recommended Intensification

• GLP-1 RA + empagliflozin + metformin: Expected A1C reduction to approximately 6.5–7.0% within 3 months 1
• Basal insulin + empagliflozin + metformin: Expected A1C reduction to approximately 6.8–7.2% within 3 months 1
• Weight loss of 2–5 kg with GLP-1 RA versus potential weight gain with insulin 1
• Minimal hypoglycemia risk with GLP-1 RA; moderate risk with insulin requiring glucose monitoring 1

Critical Monitoring Timeline

• Recheck A1C in exactly 3 months after intensification 1
• If A1C remains >7% after 3–6 months despite optimized dual therapy, add prandial insulin (if on basal insulin) or consider basal insulin (if on GLP-1 RA) 1
• Monitor for GI side effects during first 4–8 weeks after GLP-1 RA initiation 1

Common Pitfalls to Avoid

• Do not wait beyond 3 months to intensify—therapeutic inertia at A1C 8.3% increases complication risk 1
• Do not add a DPP-4 inhibitor—it provides only 0.5–0.8% A1C reduction and lacks cardiovascular benefit compared to GLP-1 RA 1
• Do not discontinue empagliflozin—its cardiovascular and renal benefits persist independent of glucose lowering 1, 2
• Do not add a sulfonylurea—it increases hypoglycemia risk without the cardiovascular benefits of GLP-1 RA or insulin 1

Target A1C After Intensification

• Aim for A1C <7.0% for most adults with type 2 diabetes 5
• Consider a less stringent target of 7.5–8.0% only if the patient has severe hypoglycemia history, limited life expectancy (<10 years), or extensive comorbidities 1, 5