How do I start and dose Jardiance (empagliflozin) for an adult with type 2 diabetes and eGFR ≥ 30 mL/min/1.73 m², including titration, monitoring, and contraindications?

Jardiance (Empagliflozin) Dosing and Management in Type 2 Diabetes

Starting Dose and Initiation Criteria

Initiate empagliflozin 10 mg once daily (taken in the morning, with or without food) if eGFR is ≥45 mL/min/1.73 m², and the dose may be increased to 25 mg once daily for additional glycemic control if needed. 1

• Do not initiate empagliflozin if eGFR is below 45 mL/min/1.73 m², as the medication is less effective for glucose lowering when renal function is impaired. 2, 1

• Both the 10 mg and 25 mg doses demonstrated cardiovascular benefit in the EMPA-REG OUTCOME trial, with no evidence of a graded dose-response for cardiovascular or renal protection. 3

Critical Renal Function Thresholds

• Assess renal function before initiating empagliflozin and monitor periodically thereafter. 1

• Discontinue empagliflozin if eGFR falls persistently below 45 mL/min/1.73 m². 1

• Empagliflozin is contraindicated in patients with eGFR less than 30 mL/min/1.73 m². 1

• More frequent renal function monitoring is recommended in patients with eGFR below 60 mL/min/1.73 m². 1

Important Nuance: Cardiovascular Benefit Below Initiation Threshold

• The cardiovascular benefit of empagliflozin appears to be present down to eGFR of 30 mL/min/1.73 m², even though initiation is not recommended below 45 mL/min/1.73 m². 2, 3

• Do not discontinue empagliflozin solely because glucose-lowering efficacy diminishes with declining renal function, as the cardiovascular and renal protective benefits persist at lower eGFR levels (down to 30 mL/min/1.73 m²). 3

Proven Clinical Benefits

Cardiovascular Outcomes

• Cardiovascular death was reduced by 38% (HR 0.62; 95% CI 0.49-0.77) in the EMPA-REG OUTCOME trial. 3

• All-cause mortality was reduced by 32% (HR 0.68; 95% CI 0.57-0.82). 3

• Heart failure hospitalization was reduced by 35% (HR 0.65; 95% CI 0.50-0.85). 3

Renal Outcomes

• Incident or worsening nephropathy occurred in 12.7% of empagliflozin patients versus 18.8% in placebo (HR 0.61; 95% CI 0.53-0.70). 4

• Doubling of serum creatinine level occurred in 1.5% of empagliflozin patients versus 2.6% in placebo, representing a 44% relative risk reduction. 4

• Renal-replacement therapy was initiated in 0.3% of empagliflozin patients versus 0.6% in placebo, representing a 55% lower relative risk. 4

Medication Adjustments When Starting Empagliflozin

• Reduce insulin dose by approximately 20% when baseline HbA1c is <8.5% to lower hypoglycemia risk. 5

• Discontinue sulfonylureas when baseline HbA1c is <8.5%. 5

• A lower dose of insulin secretagogues or insulin may be required to reduce the risk of hypoglycemia when used in combination with empagliflozin. 2, 1

• Continue ACE inhibitors or ARBs unchanged; there is no need to withhold these agents when empagliflozin is started. 5

Monitoring After Initiation

• An acute, reversible eGFR decline of approximately 2–5 mL/min/1.73 m² may occur within the first 2–4 weeks; this hemodynamic dip should not prompt discontinuation. 5

• Renal function should be evaluated prior to initiation and monitored periodically thereafter. 1

• Monitor blood glucose closely for the first 2–4 weeks, especially if insulin or other glucose-lowering agents are still being used. 5

Safety Precautions and Patient Education

Volume Depletion and Acute Kidney Injury

• Empagliflozin causes intravascular volume contraction and can cause renal impairment. 1

• Before initiating empagliflozin, consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure, and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs). 1

• Consider temporarily discontinuing empagliflozin in any setting of reduced oral intake (such as acute illness or fasting) or fluid losses (such as gastrointestinal illness or excessive heat exposure). 1

• Consider lowering concurrent loop diuretic doses, especially in elderly patients, to avoid excessive volume depletion. 5

Diabetic Ketoacidosis

• Euglycemic diabetic ketoacidosis can occur even with normal blood glucose levels (often less than 250 mg/dL) when taking empagliflozin. 1

• Factors predisposing to ketoacidosis include insulin dose reduction, acute febrile illness, reduced caloric intake due to illness or surgery, pancreatic disorders suggesting insulin deficiency, and alcohol abuse. 1

• Temporarily discontinue empagliflozin in clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or surgery). 1

• Warn patients about the possibility of euglycemic diabetic ketoacidosis and instruct them to seek immediate care for unexplained malaise, nausea, vomiting, or abdominal pain even when blood glucose is normal. 5

Genital Mycotic Infections

• Empagliflozin increases the risk for genital mycotic infections. 1

• Patients with a history of chronic or recurrent genital mycotic infections were more likely to develop genital mycotic infections. 1

• Counsel patients that genital mycotic infections occur in approximately 6% of SGLT2 inhibitor users versus 1% with placebo; advise daily hygiene to reduce risk. 5

Urinary Tract Infections

• There have been postmarketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors, including empagliflozin. 1

• Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated. 1

Contraindications

• Empagliflozin is contraindicated in patients with eGFR less than 30 mL/min/1.73 m². 1

• Empagliflozin is contraindicated in patients with a previous serious hypersensitivity reaction to empagliflozin or any of the excipients. 1

Common Pitfalls to Avoid

• Do not discontinue empagliflozin when eGFR falls below 45 mL/min/1.73 m² if the patient is already on treatment, as cardiovascular and renal benefits persist despite reduced glucose-lowering efficacy. 3

• Do not stop empagliflozin in response to the expected early eGFR dip (2–5 mL/min/1.73 m²) observed in the first 2–4 weeks; this change is hemodynamic and reversible. 5

• Do not reduce the empagliflozin dose below 10 mg for cardiovascular or renal indications, even at lower eGFR levels; all outcome trials used the fixed 10 mg or 25 mg doses. 5

• Do not fail to monitor for volume depletion, especially when combined with diuretics. 6

• Do not overlook the need for sick day protocols during acute illness; consider temporarily withholding empagliflozin during acute illness, prolonged fasting, or surgical procedures. 6