Can a patient with diabetes on Jardiance (empagliflozin), glipizide, and metformin, with an elevated Hemoglobin A1c level, be safely treated?

Can This Patient Be Safely Treated? Yes, But Immediate Medication Adjustment Is Required

This patient on Jardiance (empagliflozin), glipizide, metformin with an HbA1c of 8.0% requires immediate treatment intensification, specifically by adding a GLP-1 receptor agonist and reducing or discontinuing the glipizide to minimize hypoglycemia risk while achieving better glycemic control. 1, 2

Critical Safety Concern: Hypoglycemia Risk

The current regimen combines an SGLT2 inhibitor (Jardiance) with a sulfonylurea (glipizide), which creates significant hypoglycemia risk:

• Sulfonylureas combined with SGLT2 inhibitors increase severe hypoglycemia rates in cardiovascular outcomes trials, despite SGLT2 inhibitors alone not causing hypoglycemia 1
• When adding SGLT2 inhibitors to patients already on sulfonylureas and meeting glycemic targets, reducing or withdrawing the sulfonylurea dose is necessary to prevent hypoglycemia 1
• This patient's HbA1c of 8.0% indicates they are NOT at glycemic target (goal <7.0% for most patients), yet the sulfonylurea poses unnecessary hypoglycemia risk 1

Recommended Treatment Algorithm

Step 1: Discontinue or Reduce Glipizide Immediately

• Stop glipizide entirely since the patient needs additional glucose lowering (HbA1c 8.0%), and sulfonylureas provide minimal cardiovascular benefit while increasing hypoglycemia risk 1
• The American Diabetes Association guidelines indicate that for patients requiring intensification, sulfonylureas should be replaced with agents offering cardiovascular protection 1, 2

Step 2: Add GLP-1 Receptor Agonist

• Initiate a GLP-1 receptor agonist with proven cardiovascular benefit (liraglutide 1.8 mg daily is preferred based on strongest evidence) 1
• GLP-1 receptor agonists provide HbA1c reduction of 0.6-0.8% when added to existing therapy, which would bring this patient close to target 2
• This class offers cardiovascular mortality reduction in patients with type 2 diabetes and established ASCVD 1
• Minimal hypoglycemia risk when used without sulfonylureas or insulin 1, 2

Step 3: Continue Metformin and Jardiance

• Maintain metformin as foundation therapy unless contraindicated (eGFR <30 mL/min/1.73 m²) 1
• Continue Jardiance (empagliflozin) for its proven cardiovascular and renal benefits, independent of glucose-lowering effects 1
• Empagliflozin reduces cardiovascular death and heart failure hospitalization, with benefits observed even at eGFR as low as 30-44 mL/min/1.73 m² 1

Monitoring Requirements After Adjustment

Within First 2-4 Weeks:

• Assess volume status due to SGLT2 inhibitor's diuretic effect; watch for symptoms of volume depletion, especially if patient takes other diuretics 1
• Monitor for GLP-1 receptor agonist side effects, primarily gastrointestinal (nausea, vomiting, diarrhea) 1
• Check for genital mycotic infections, which occur in 11-14% of women and 7-8% of men on SGLT2 inhibitors 1, 3

At 3 Months:

• Recheck HbA1c to assess treatment effectiveness; target <7.0% for most patients 1, 2
• Monitor renal function (eGFR and albuminuria) as both metformin and empagliflozin require monitoring 1
• Assess vitamin B12 levels if metformin use exceeds 4 years 1

Expected eGFR Changes:

• Expect modest initial eGFR decline (hemodynamic, reversible) within first weeks of SGLT2 inhibitor use 1
• This initial decline is NOT an indication to discontinue therapy, as long-term eGFR preservation occurs with continuation 1
• Continue empagliflozin even if eGFR falls below 30 mL/min/1.73 m² unless poorly tolerated or kidney replacement therapy is imminent 1

Critical Pitfalls to Avoid

Do Not Continue Sulfonylurea:

• Glipizide provides no cardiovascular benefit and significantly increases hypoglycemia risk, particularly when combined with SGLT2 inhibitors 1, 4
• Empagliflozin was superior to glimepiride (another sulfonylurea) for HbA1c reduction at 104 weeks (-0.11% difference, p=0.0153), with only 2% hypoglycemia rate versus 24% with glimepiride 4

Do Not Delay Treatment Intensification:

• Waiting beyond 3 months at HbA1c above target increases complication risk 2
• The American Diabetes Association recommends reassessing after 3 months and intensifying if target not achieved 1

Do Not Discontinue SGLT2 Inhibitor for Initial eGFR Dip:

• The modest initial eGFR reduction is hemodynamic and reversible, not indicative of kidney injury 1
• Long-term kidney protection occurs despite this initial decline 1

Special Considerations for This Regimen

Why This Patient Needs Intensification:

• HbA1c 8.0% is above target (<7.0% for most patients to reduce microvascular complications) 1
• Current triple therapy (metformin + SGLT2i + sulfonylurea) is suboptimal because sulfonylureas lack cardiovascular benefit 1

Cardiovascular Risk Reduction Priority:

• For patients with type 2 diabetes, SGLT2 inhibitors and GLP-1 receptor agonists with demonstrated cardiovascular benefit are recommended independent of HbA1c and independent of metformin use 1
• The cardiovascular benefits of empagliflozin are out of proportion to HbA1c reduction, suggesting mechanisms beyond glucose lowering 1

Cost Considerations:

• GLP-1 receptor agonists are expensive (median monthly cost $2,036 for liraglutide 1.8 mg) 1
• Discuss out-of-pocket costs with patient before initiating, as financial burden may affect adherence 1
• However, cardiovascular benefits justify the expense in appropriate patients 1

Summary of Safe Treatment Plan

The patient can be safely treated with immediate modification: discontinue glipizide, add GLP-1 receptor agonist (liraglutide preferred), and continue metformin plus Jardiance. This approach eliminates hypoglycemia risk from the sulfonylurea, provides additional HbA1c reduction of 0.6-0.8%, and maximizes cardiovascular protection through dual cardioprotective agents (SGLT2i + GLP-1 RA). 1, 2