How should I initiate empagliflozin (Jardiance) in an adult with type 2 diabetes mellitus inadequately controlled on metformin, including starting dose, titration, contraindications, and monitoring?

Starting Jardiance (Empagliflozin) in Type 2 Diabetes

Start empagliflozin 10 mg once daily in the morning with or without food, and do not increase the dose beyond 10 mg unless the patient has heart failure requiring higher dosing, as the 25 mg dose provides no additional glycemic benefit but increases cost. 1

Pre-Initiation Assessment

Before starting empagliflozin, you must check the following:

• Measure eGFR and do not initiate if eGFR is below 45 mL/min/1.73 m² for glycemic control, or below 20 mL/min/1.73 m² for heart failure indications. 2, 1 The FDA label states contraindication for severe renal impairment, end-stage renal disease, or dialysis. 1

• Assess volume status, particularly in elderly patients, those with low systolic blood pressure, patients on diuretics, or those with existing renal impairment. 2, 1 Correct any volume depletion before initiating therapy to reduce hypotension risk.

• Screen for history of serious hypersensitivity reactions to empagliflozin, as this is an absolute contraindication. 1

Starting Dose and Administration

• The recommended starting dose is empagliflozin 10 mg once daily, taken in the morning, with or without food. 1 This is both the starting and maintenance dose for most patients with type 2 diabetes.

• The dose may be increased to 25 mg once daily, but this higher dose does not provide additional glucose-lowering efficacy and should only be considered for specific cardiovascular or heart failure indications. 2, 1 Research shows that both 10 mg and 25 mg doses produce similar HbA1c reductions of approximately 0.7-0.8%. 3, 4

Dose Adjustments Based on Renal Function

The ADA/KDIGO consensus provides clear guidance on eGFR-based dosing:

• eGFR ≥45 mL/min/1.73 m²: Use standard 10 mg daily dose without adjustment. 2

• eGFR 30-44 mL/min/1.73 m² (Stage 3b CKD): Continue 10 mg daily if already on therapy; do not initiate for glycemic control but may initiate for heart failure if eGFR ≥20. 2

• eGFR <30 mL/min/1.73 m² (Stage 4 CKD): Do not initiate; discontinue if eGFR falls persistently below this threshold. 2, 1 The exception is heart failure patients where continuation may be considered down to eGFR 20 mL/min/1.73 m² for cardiovascular and kidney benefits. 2

Medication Adjustments at Initiation

You generally do not need to adjust background diabetes medications when starting empagliflozin, but follow-up within 2-4 weeks is essential to reassess glycemia and volume status. 2 However, specific situations require proactive dose reduction:

• If the patient is taking insulin or a sulfonylurea, consider reducing their dose by 10-20% to minimize hypoglycemia risk, though empagliflozin itself does not cause hypoglycemia. 5, 1 Research shows confirmed hypoglycemia occurred in only 2% of patients on empagliflozin versus 24% on glimepiride. 3

• Do not discontinue metformin when adding empagliflozin; continue metformin at maximum tolerated dose unless contraindicated. 6, 5

Monitoring Requirements

Monitor the following parameters after initiating empagliflozin:

• Check eGFR at least annually if baseline eGFR ≥60 mL/min/1.73 m², and every 3-6 months if eGFR is 45-60 mL/min/1.73 m². 2, 7 Discontinue if eGFR falls persistently below 45 mL/min/1.73 m². 1

• Assess volume status and blood pressure at follow-up visits, especially in the first few weeks. 2, 1 Empagliflozin reduces systolic blood pressure by approximately 4 mmHg and diastolic by 2 mmHg. 8, 4

• Check HbA1c every 3 months until glycemic targets are achieved. 6 If HbA1c remains above goal after 3 months at maximum tolerated metformin plus empagliflozin, add a third agent immediately. 6

• Monitor for genital mycotic infections, particularly in women, where incidence is approximately 6% versus 1% with placebo. 2 Daily hygiene measures may reduce this risk. 2

• Monitor LDL-C as empagliflozin may cause modest increases; treat as appropriate. 1

Critical Safety Warnings and When to Hold Therapy

Educate patients to temporarily discontinue empagliflozin during acute illness, surgery, or periods of reduced oral intake to prevent euglycemic diabetic ketoacidosis (DKA). 2, 1 This is particularly important for patients on insulin, who are at highest risk. 2

• If the patient develops signs of metabolic acidosis (nausea, vomiting, abdominal pain, malaise, dyspnea) regardless of blood glucose level, check blood or urine ketones immediately and discontinue empagliflozin if ketoacidosis is confirmed. 2, 1 Euglycemic DKA can occur with minimal glucose elevation. 2

• Consider temporarily discontinuing empagliflozin in settings of acute kidney injury, severe dehydration, or before procedures requiring iodinated contrast. 2, 1

• If signs of urosepsis or pyelonephritis develop, evaluate and treat promptly. 1 Though urinary tract infections occur at similar rates to placebo (approximately 8-10%), serious infections require immediate attention. 4

Special Populations

In elderly patients, the risk of volume depletion and hypotension is higher; start with careful volume assessment and closer monitoring. 1, 8 However, do not avoid empagliflozin solely based on age, as cardiovascular and renal benefits are preserved. 2

Advise women of reproductive potential about potential fetal risks, especially during the second and third trimesters; empagliflozin is not recommended during pregnancy. 1

Empagliflozin is not recommended while breastfeeding. 1

Common Pitfalls to Avoid

• Do not delay adding empagliflozin in patients with established cardiovascular disease, heart failure, or CKD regardless of current HbA1c level, as mortality and morbidity benefits are independent of glycemic control. 6, 5 The ADA/KDIGO consensus strongly recommends SGLT2 inhibitors with proven kidney or cardiovascular benefit for patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m². 2

• Do not increase to 25 mg solely for better glucose control, as both doses produce equivalent HbA1c reductions. 2, 3 The higher dose is reserved for heart failure indications where studied. 2

• Do not discontinue empagliflozin if eGFR declines below 45 mL/min/1.73 m² after initiation; continue for cardiovascular and kidney benefits until eGFR falls below 20-30 mL/min/1.73 m² depending on indication. 2 Once initiated, empagliflozin can be continued at lower eGFR levels than initiation thresholds. 2

• Do not fail to counsel patients about genital hygiene and the increased risk of mycotic infections, particularly in women. 2 Most infections are easily treated, but rare cases of Fournier gangrene have been reported. 2