Can Jardiance (empagliflozin) and Glipizide be used together?

Empagliflozin (Jardiance) and Glipizide Can Be Used Together in Type 2 Diabetes Management

Yes, empagliflozin (Jardiance) and glipizide can be used together as they have complementary mechanisms of action, but careful monitoring for hypoglycemia is required as this combination increases hypoglycemia risk. 1

Mechanism Rationale for Combination

• Empagliflozin (SGLT2 inhibitor): Works by inhibiting glucose reabsorption in the kidneys, causing glucosuria (glucose excretion in urine)
• Glipizide (Sulfonylurea): Stimulates insulin secretion from pancreatic beta cells

This combination provides complementary glucose-lowering effects through insulin-independent and insulin-dependent mechanisms.

Benefits of This Combination

1. Enhanced glycemic control: The combination can help patients achieve glycemic targets when monotherapy is insufficient
2. Cardiovascular benefits: Empagliflozin provides cardiovascular protection that glipizide does not offer 1
3. Different mechanisms: Addresses multiple pathophysiological defects in type 2 diabetes

Important Precautions

Hypoglycemia Risk

• The risk of hypoglycemia is significantly increased when SGLT2 inhibitors like empagliflozin are used with sulfonylureas like glipizide 2
• Consider reducing glipizide dose when initiating empagliflozin to minimize hypoglycemia risk 1
• Patients should be educated about recognizing and managing hypoglycemia

Renal Function Considerations

• eGFR monitoring is essential:
  • Empagliflozin is not recommended when eGFR <45 mL/min/1.73 m² 1
  • For glipizide, initiate conservatively (e.g., 2.5 mg once daily) and titrate slowly with eGFR <45 mL/min/1.73 m² 1
• Renal function should be evaluated prior to initiation and monitored periodically 2

Other Safety Considerations

• Genital mycotic infections: Empagliflozin increases risk, especially in women 1, 2
• Euglycemic diabetic ketoacidosis: Monitor for and temporarily discontinue empagliflozin during illness, surgery, or fasting 2
• Volume depletion: Empagliflozin can cause intravascular volume contraction 2

Dosing Recommendations

1. Starting doses:

   • Empagliflozin: 10 mg once daily 1
   • Glipizide: Consider lower starting dose (2.5 mg) when used with empagliflozin 1

2. Dose adjustments:

   • Titrate glipizide slowly to avoid hypoglycemia
   • Empagliflozin can be increased to 25 mg daily if needed and tolerated 1

Monitoring Recommendations

• Blood glucose: Regular monitoring to assess efficacy and detect hypoglycemia
• Renal function: Check eGFR before starting and periodically during treatment
• Hypoglycemia symptoms: Educate patients about recognition and management
• Genital symptoms: Monitor for mycotic infections
• Signs of volume depletion: Particularly in elderly patients or those on diuretics

Alternative Combinations to Consider

If this combination is not appropriate, consider:

• Empagliflozin + GLP-1 receptor agonist: Lower hypoglycemia risk with complementary cardiovascular benefits 1
• Metformin + empagliflozin: First-line combination with low hypoglycemia risk 1

Clinical Pitfalls to Avoid

1. Not reducing sulfonylurea dose when adding empagliflozin
2. Overlooking renal function before and during treatment
3. Failing to educate patients about hypoglycemia symptoms and management
4. Not considering cardiovascular risk when selecting antidiabetic medications
5. Continuing both medications during acute illness or prolonged fasting

The combination of empagliflozin and glipizide can be effective for glycemic control in type 2 diabetes when used appropriately with careful monitoring for hypoglycemia and other potential adverse effects.