Which medications need to be stopped or dose‑adjusted when starting empagliflozin (Jardiance) in a patient already on another sodium‑glucose co‑transporter‑2 inhibitor, insulin or sulfonylureas, and a loop or thiazide diuretic?

Medication Adjustments When Starting Jardiance (Empagliflozin)

When initiating Jardiance, you must stop any other SGLT2 inhibitor immediately, reduce sulfonylurea doses by 50% (or discontinue if HbA1c is well-controlled), reduce basal insulin by approximately 20%, and consider lowering loop or thiazide diuretic doses to prevent excessive volume depletion. 1

Medications That Must Be Stopped

Other SGLT2 Inhibitors

• Discontinue any concurrent SGLT2 inhibitor completely (e.g., dapagliflozin, canagliflozin, ertugliflozin) as these medications are in the same drug class and should never be combined 1

DPP-4 Inhibitors (if switching to a GLP-1 receptor agonist alongside Jardiance)

• If you plan to add a GLP-1 receptor agonist for additional cardiovascular protection, discontinue any DPP-4 inhibitor (e.g., sitagliptin, linagliptin) before starting the GLP-1 RA 1
• DPP-4 inhibitors can continue if only Jardiance is being added 1

Medications Requiring Dose Reduction

Sulfonylureas (High Priority)

• Reduce sulfonylurea dose by 50% when starting Jardiance if HbA1c is well-controlled at baseline or if the patient has a history of frequent hypoglycemic events 1
• Discontinue sulfonylureas entirely if the patient is already on a minimal dose or if HbA1c is <8.5% 1
• The maximum recommended dose after reduction should be no more than 50% of the maximum labeled dose 1
• Examples: If on glipizide 10 mg twice daily, reduce to 5 mg twice daily; if on glyburide 10 mg daily, reduce to 5 mg daily 1

Insulin

• Reduce total daily insulin dose by approximately 20% when starting Jardiance if HbA1c is well-controlled or if there is a history of frequent hypoglycemia 1
• Avoid substantial initial reductions greater than 20%, as this increases the risk of euglycemic diabetic ketoacidosis 1
• Patients on complex insulin regimens or with "brittle" diabetes should have Jardiance initiated in collaboration with their diabetes care provider 1
• Never completely stop insulin in insulin-requiring patients, even when holding Jardiance during illness, as complete cessation significantly elevates ketoacidosis risk 1

Loop and Thiazide Diuretics

• Consider reducing diuretic doses to prevent excessive volume depletion, particularly in elderly patients or those already on diuretic therapy 1
• The diuretic effect of Jardiance is additive with loop diuretics, creating potentially significant natriuretic effects 1
• Monitor for orthostatic lightheadedness, weakness, and signs of volume depletion 1
• In clinical practice, a 25-50% reduction in loop diuretic dose is reasonable when initiating Jardiance in patients at high risk for volume depletion 2, 3

Medications That Can Continue Unchanged

ACE Inhibitors and ARBs

• Continue ACE inhibitors or ARBs without dose adjustment when starting Jardiance 1
• Use clinical judgment if simultaneously initiating or up-titrating these agents in patients with impaired renal function 1
• More than 99% of patients in major SGLT2 inhibitor trials were on renin-angiotensin system blockers, demonstrating safety of the combination 1

Metformin

• Continue metformin at current dose if eGFR ≥60 mL/min/1.73 m² 1
• No preemptive dose reduction is needed when adding Jardiance to metformin 1

Critical Monitoring in the First 4 Weeks

• Instruct patients to monitor glucose closely at home for the first 3-4 weeks after starting Jardiance, especially if on insulin or sulfonylureas 1
• Recheck eGFR within 1-2 weeks; an acute, reversible decline of 2-5 mL/min/1.73 m² is expected and should not prompt discontinuation 1
• Assess volume status at follow-up visits, particularly in elderly patients or those on diuretics 1

Patient Education Requirements

Hypoglycemia Risk

• Educate patients taking insulin or sulfonylureas about increased hypoglycemia risk when adding Jardiance 1
• The risk is not significantly increased in patients not taking insulin or sulfonylureas 1

Volume Depletion

• Educate patients about symptoms of low blood pressure: lightheadedness, orthostasis, weakness 1
• Elderly patients and those on diuretics should be especially vigilant 1, 3

Diabetic Ketoacidosis

• Warn about euglycemic diabetic ketoacidosis, which can occur even with blood glucose readings in the 150-250 mg/dL range 1
• Symptoms include nausea, vomiting, abdominal pain, and generalized weakness 1
• Hold Jardiance during acute illness with reduced oral intake, fever, vomiting, or diarrhea 1
• Stop Jardiance at least 3 days before major surgery or procedures requiring prolonged fasting 1

Genital Infections

• Genital mycotic infections occur in approximately 6% of SGLT2 inhibitor users versus 1% with placebo 1, 3
• Emphasize meticulous genital hygiene to lower risk 1

Common Pitfalls to Avoid

• Do not discontinue Jardiance when eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist even though glucose-lowering efficacy diminishes 1
• Do not stop Jardiance because of the expected initial eGFR dip in the first 2-4 weeks; this change is hemodynamic and reversible 1
• Do not combine Jardiance with sulfonylureas without dose reduction, as this significantly increases hypoglycemia risk 1
• Do not reduce insulin doses by more than 20% initially, as excessive reductions increase ketoacidosis risk 1