What are the prescribing recommendations for Jardiance (empagliflozin) in adults with type 2 diabetes, including indications, dosing, renal function limits, contraindications, monitoring, and alternative therapies?

Jardiance (Empagliflozin) Prescribing Recommendations

Primary Indications

Jardiance is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, and to reduce the risk of cardiovascular death in adult patients with type 2 diabetes and established cardiovascular disease. 1

Standard Dosing

• Start with 10 mg once daily, taken in the morning, with or without food. 1
• The dose may be increased to 25 mg once daily if additional glycemic control is needed. 1
• Both doses (10 mg and 25 mg) demonstrated cardiovascular benefits in the EMPA-REG OUTCOME trial, with no dose titration required for cardiovascular protection. 2

Renal Function Requirements and Monitoring

• Assess renal function (eGFR) before initiating Jardiance. 1
• Do not initiate Jardiance if eGFR is below 45 mL/min/1.73 m². 1
• Discontinue Jardiance if eGFR falls persistently below 45 mL/min/1.73 m². 1
• The glucose-lowering efficacy of Jardiance decreases with declining renal function, although cardiovascular benefits appear to persist down to eGFR of 30 mL/min/1.73 m². 2

Absolute Contraindications

• History of serious hypersensitivity reaction to empagliflozin or any excipients in Jardiance. 1
• Severe renal impairment, end-stage renal disease, or dialysis. 1

Critical Safety Precautions and Monitoring

Volume Depletion and Hypotension

• Before initiating Jardiance, assess and correct volume status in patients with renal impairment, the elderly, patients with low systolic blood pressure, and patients on diuretics. 1
• Monitor for signs and symptoms of hypotension during therapy. 1
• Higher incidence of adverse reactions related to volume depletion occurs in geriatric patients and those with renal impairment. 1

Ketoacidosis Risk

• Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. 1
• If ketoacidosis is suspected, discontinue Jardiance immediately, evaluate and treat promptly. 1
• Before initiating Jardiance, consider risk factors for ketoacidosis. 1
• Patients on Jardiance may require monitoring and temporary discontinuation in clinical situations known to predispose to ketoacidosis. 1

Acute Kidney Injury

• Consider temporarily discontinuing Jardiance in settings of reduced oral intake or fluid losses. 1
• If acute kidney injury occurs, discontinue Jardiance and promptly treat. 1
• Monitor renal function during therapy. 1

Urinary Tract Infections

• Evaluate patients for signs and symptoms of urinary tract infections (including urosepsis and pyelonephritis) and treat promptly if indicated. 1

Hypoglycemia Prevention

• Consider lowering the dose of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating Jardiance. 1
• Jardiance carries a low inherent risk of hypoglycemia due to its insulin-independent mechanism of action, but hypoglycemia can occur when combined with insulin or sulfonylureas. 3, 4

Genital Mycotic Infections

• Monitor for genital mycotic infections and treat as appropriate. 1
• Female genital mycotic infections are among the most common adverse reactions (≥5% incidence). 1

Hypersensitivity Reactions

• If hypersensitivity reactions occur, discontinue Jardiance, treat promptly, and monitor until signs and symptoms resolve. 1

Lipid Monitoring

• Monitor LDL-C and treat as appropriate, as Jardiance may increase LDL cholesterol. 1

Special Populations

Pregnancy

• Advise females of the potential risk to a fetus, especially during the second and third trimesters. 1

Lactation

• Jardiance is not recommended when breastfeeding. 1

Geriatric Patients

• Higher incidence of adverse reactions related to volume depletion and reduced renal function occurs in elderly patients. 1

Patients with Renal Impairment

• Higher incidence of adverse reactions related to reduced renal function occurs in this population. 1

Cardiovascular and Renal Benefits

• In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of major adverse cardiovascular events (3-point MACE) by 14% (HR 0.86,95% CI 0.74-0.99) in patients with type 2 diabetes and established cardiovascular disease. 2
• Cardiovascular death was reduced by 38% (HR 0.62,95% CI 0.49-0.77). 2
• All-cause mortality was reduced by 32% (HR 0.68,95% CI 0.57-0.82). 2
• Heart failure hospitalization was reduced by 35% (HR 0.65,95% CI 0.50-0.85). 2
• Empagliflozin slowed progression of kidney disease, with incident or worsening nephropathy occurring in 12.7% of empagliflozin-treated patients versus 18.8% of placebo patients (HR 0.61,95% CI 0.53-0.70). 5
• Doubling of serum creatinine occurred in 1.5% of empagliflozin patients versus 2.6% of placebo patients, representing a 44% relative risk reduction. 5

Alternative SGLT2 Inhibitors

• Canagliflozin (100-300 mg daily) is an alternative SGLT2 inhibitor with similar cardiovascular benefits, though it requires dose adjustment for eGFR 45-59 mL/min/1.73 m² (do not exceed 100 mg/day). 2
• Canagliflozin has been associated with increased risk of amputation and bone fractures, which has not been observed with empagliflozin. 3
• Dapagliflozin is another SGLT2 inhibitor option, though it was not included in the primary guideline evidence for Jardiance-specific recommendations. 6

Common Pitfalls to Avoid

• Do not continue Jardiance if eGFR persistently falls below 45 mL/min/1.73 m², as efficacy is significantly reduced and safety concerns increase. 1
• Do not overlook volume status assessment before initiation, particularly in elderly patients or those on diuretics. 1
• Do not ignore signs of ketoacidosis even when blood glucose levels are normal (euglycemic DKA). 1
• Do not forget to reduce insulin or sulfonylurea doses when adding Jardiance to prevent hypoglycemia. 1