In an adult with type 2 diabetes who is taking glipizide, can I add Jardiance (empagliflozin) and how should the doses be adjusted and monitored?

Adding Jardiance (Empagliflozin) to Glipizide in Type 2 Diabetes

Yes, you can add Jardiance (empagliflozin) to glipizide, but you must reduce the glipizide dose by 50% immediately to prevent hypoglycemia. 1

Immediate Dose Adjustments Required

When adding empagliflozin to a patient already taking glipizide (a sulfonylurea), the following adjustments are mandatory:

• Reduce glipizide dose by 50% at the time empagliflozin is initiated, or discontinue glipizide entirely if the patient is already on a minimal dose. 1
• If the patient is on glipizide doses at or near maximum (typically >10 mg daily), reduce to no more than 50% of the maximum recommended dose. 1
• This dose reduction is critical because the combination significantly increases hypoglycemia risk compared to either agent alone. 1

Empagliflozin Dosing

• Start empagliflozin 10 mg once daily in the morning, with or without food. 2
• The dose may be increased to 25 mg once daily if additional glycemic control is needed after at least 4 weeks. 2
• Do not initiate empagliflozin if eGFR is below 45 mL/min/1.73 m² for glycemic control purposes. 2, 1
• Discontinue empagliflozin if eGFR falls persistently below 45 mL/min/1.73 m². 2

Critical Monitoring During the First 3-4 Weeks

Patients must be counseled to self-monitor blood glucose levels closely during the first 3-4 weeks after initiating empagliflozin, particularly because the combination with glipizide increases hypoglycemia risk. 1

Specific monitoring parameters include:

• Daily fasting glucose checks to guide further glipizide dose adjustments. 1
• Immediate glucose testing if symptoms of hypoglycemia occur (tremor, sweating, confusion, dizziness). 1
• If hypoglycemia occurs, reduce glipizide dose by an additional 10-20% and identify the precipitating cause. 1
• Monitor for signs of volume depletion (orthostatic lightheadedness, dizziness), especially in elderly patients or those on diuretics. 1

Renal Function Assessment

• Check eGFR before initiating empagliflozin to confirm eligibility. 2, 1
• Empagliflozin causes a modest, reversible decrease in eGFR in the first several weeks; recheck renal function 2-4 weeks after initiation, particularly in patients with baseline eGFR 45-60 mL/min/1.73 m². 1
• Continue monitoring eGFR every 3-6 months thereafter. 1

Patient Education on Key Adverse Effects

Genital Mycotic Infections

• Inform patients about the higher risk of genital mycotic infections (occurs in ~6% of patients), which can be reduced with meticulous personal hygiene. 1, 3
• Treat initial infections with topical antifungal agents; oral antifungals may be used but require attention to QTc prolongation if the patient is on antiarrhythmic drugs. 1

Euglycemic Diabetic Ketoacidosis

• Educate patients about the unlikely but serious risk of euglycemic diabetic ketoacidosis (DKA), which can occur even with normal blood glucose levels. 1, 2
• Advise patients to seek immediate medical care if they develop nausea, vomiting, abdominal pain, or generalized weakness. 1
• Withhold empagliflozin during prolonged fasting, surgery, or critical illness when patients are at greater risk for ketosis. 1

Volume Depletion

• Patients should be advised about the diuretic effect of empagliflozin and potentially additive natriuretic effects when combined with loop diuretics. 1
• Elderly patients or those on diuretic therapy should monitor for orthostatic lightheadedness and contact their clinician if symptoms occur. 1

Expected Clinical Benefits

Beyond glucose lowering, empagliflozin provides:

• Weight loss of 1.5-3.5 kg over 24-52 weeks. 3, 4
• Systolic blood pressure reduction of 3-5 mmHg. 1, 3
• Cardiovascular and renal protection independent of glycemic control, particularly important in patients with established cardiovascular disease or chronic kidney disease. 1, 5

Reassessment Timeline

• Recheck HbA1c at 3 months after adding empagliflozin to evaluate treatment effectiveness. 1
• If HbA1c remains above target after 3 months of optimized therapy, consider discontinuing glipizide entirely and adding a GLP-1 receptor agonist instead, which provides superior cardiovascular benefit without hypoglycemia risk. 1

Key Pitfalls to Avoid

• Do not continue full-dose glipizide when adding empagliflozin; the hypoglycemia risk is unacceptably high. 1
• Do not initiate empagliflozin if eGFR <45 mL/min/1.73 m² for glycemic purposes, though it may be continued for cardiovascular/renal protection down to eGFR ≥25 mL/min/1.73 m² if already established. 1, 2
• Do not ignore the initial eGFR dip in the first 2-4 weeks; this is typically reversible and does not necessitate discontinuation unless eGFR falls persistently below 45 mL/min/1.73 m². 1
• Do not combine empagliflozin with DPP-4 inhibitors and GLP-1 receptor agonists simultaneously; concurrent use of DPP-4 inhibitors with GLP-1 agonists provides no additional benefit. 1