Empagliflozin

Empagliflozin is a high-affinity, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated for the management of type 2 diabetes mellitus, heart failure, and chronic kidney disease. By blocking glucose reabsorption in the proximal tubule, it promotes glucosuria and induces beneficial metabolic and hemodynamic effects. Its use is supported by robust outcome trials demonstrating significant reductions in cardiovascular mortality and hospitalization for heart failure, as well as delaying the progression of renal disease. This agent represents a paradigm shift in the therapeutic approach, moving beyond glycemic control to address multisystem organ protection.

Features

• Selective inhibition of SGLT2 in the proximal renal tubules
• Once-daily oral dosing, independent of meals
• Available in 10 mg and 25 mg film-coated tablets
• Linear pharmacokinetics with dose-proportional exposure
• Extensive plasma protein binding (>99%)
• Metabolized primarily via glucuronidation by UGT enzymes
• Mean elimination half-life of approximately 12–13 hours

Benefits

• Reduces HbA1c by promoting urinary glucose excretion
• Lowers systolic and diastolic blood pressure through natriuresis and osmotic diuresis
• Demonstrates cardiovascular mortality benefit in patients with established cardiovascular disease
• Decreases risk of hospitalization for heart failure in both diabetic and non-diabetic populations
• Slows progression of chronic kidney disease by reducing albuminuria and preserving eGFR
• Contributes to modest weight loss through caloric loss via glycosuria

Common use

Empagliflozin is approved for use in adults with type 2 diabetes mellitus to improve glycemic control, as an adjunct to diet and exercise. It is also indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. Additionally, it is approved for the treatment of heart failure with reduced ejection fraction (HFrEF) and for reducing the risk of sustained decline in eGFR, progression to end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression.

Dosage and direction

The recommended starting dose is 10 mg orally once daily, taken with or without food. In patients tolerating 10 mg once daily who require additional glycemic control, the dose may be increased to 25 mg once daily. For heart failure and chronic kidney disease indications, the recommended dose is 10 mg once daily. Dose adjustment is not required based on age, gender, race, or body weight. Renal function should be assessed prior to initiation and periodically during treatment; use is not recommended when eGFR is persistently below 20 mL/min/1.73m² for diabetes indications, or below 20 mL/min/1.73m² for cardiorenal indications.

Precautions

Monitor renal function before initiation and periodically thereafter. Assess volume status and correct volume depletion before starting. Consider temporary interruption in situations of reduced oral intake or fluid loss. Monitor for signs and symptoms of urinary tract infections and genital mycotic infections. Evaluate patients for history of ketoacidosis, even in the presence of normal or only mildly elevated blood glucose levels. Monitor hemoglobin/hematocrit at initiation and as clinically indicated. Not recommended during the second and third trimesters of pregnancy. Use with caution in elderly patients and those on diuretics or with low systolic blood pressure.

Contraindications

History of serious hypersensitivity reaction to empagliflozin or any excipient in the formulation. Patients with severe renal impairment (eGFR <30 mL/min/1.73m²), end-stage renal disease, or those on dialysis, when prescribed for diabetes management. Concomitant use with other SGLT2 inhibitors is contraindicated.

Possible side effects

Common adverse reactions (≥2%) include urinary tract infections, female genital mycotic infections, upper respiratory tract infections, increased urination, thirst, and nausea. Serious adverse reactions may include ketoacidosis, acute kidney injury, urosepsis and pyelonephritis, hypoglycemia (when used with insulin or insulin secretagogues), necrotizing fasciitis of the perineum (Fournier’s gangrene), and hypersensitivity reactions. Volume depletion-related events such as hypotension and dizziness may occur, particularly in elderly patients and those on diuretics.

Drug interaction

No clinically significant interactions with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, simvastatin, or oral contraceptives. May enhance the hypoglycemic effect of insulin and insulin secretagogues, requiring dose reduction of these agents. Diuretics may enhance the potential for volume depletion. Inducers of UGT enzymes (e.g., rifampin, phenytoin, ritonavir) may decrease empagliflozin exposure.

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. If the missed dose is not remembered until the next day, the missed dose should be skipped and the regular dosing schedule resumed. Do not take a double dose to make up for a missed dose.

Overdose

In the event of overdose, contact Poison Control or seek emergency medical attention. Expected signs and symptoms may include hypoglycemia and dehydration-related events such as dizziness, hypotension, and tachycardia. Management should include supportive measures and symptomatic treatment. Removal of empagliflozin by hemodialysis has not been studied, but is unlikely to be effective due to high protein binding.

Storage

Store at room temperature between 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Keep in the original container to protect from moisture. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging.

Disclaimer

This information is intended for healthcare professionals and should not replace professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in this product card. The prescribing physician should be consulted regarding any changes in dosage regimen or potential drug interactions.

Reviews

Clinical trials and real-world evidence consistently demonstrate empagliflozin’s efficacy in reducing cardiovascular events and preserving renal function. The EMPA-REG OUTCOME trial showed a 38% reduction in cardiovascular death and 35% reduction in hospitalization for heart failure. The EMPEROR-Reduced and EMPEROR-Preserved trials confirmed benefits in heart failure across the ejection fraction spectrum. EMPA-KIDNEY demonstrated a 28% reduction in risk of kidney disease progression. Post-marketing surveillance supports the favorable benefit-risk profile, with most adverse events being manageable and consistent with the known safety profile. Many experts consider empagliflozin a foundational therapy in modern cardiorenal medicine.