Empagliflozin

Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated for the management of type 2 diabetes mellitus, heart failure, and chronic kidney disease. By selectively inhibiting SGLT2 in the proximal renal tubules, it reduces renal glucose reabsorption and promotes glycosuria, thereby lowering plasma glucose concentrations. Its therapeutic benefits extend beyond glycemic control to include significant cardiovascular and renal risk reduction, positioning it as a cornerstone therapy in modern evidence-based treatment algorithms for cardiometabolic and renal conditions.

Features

• Active pharmaceutical ingredient: Empagliflozin
• Pharmacologic class: Sodium-glucose cotransporter 2 (SGLT2) inhibitor
• Available formulations: Oral tablets (10 mg and 25 mg)
• Mechanism of action: Selective and reversible inhibition of SGLT2 in the proximal convoluted tubule
• Bioavailability: Approximately 78%
• Half-life: ~12–13 hours
• Time to peak plasma concentration: 1.5–2.5 hours post-administration
• Excretion: Primarily fecal (54.4%) and renal (40.9%)
• Pregnancy category: Not recommended during second and third trimesters

Benefits

• Reduces HbA1c by promoting urinary glucose excretion without stimulating insulin secretion
• Lowers risk of major adverse cardiovascular events, including cardiovascular death, in patients with established cardiovascular disease
• Decreases hospitalization for heart failure in both diabetic and non-diabetic populations
• Slows progression of chronic kidney disease and reduces albuminuria
• Promotes modest weight loss and blood pressure reduction through osmotic diuresis and caloric loss
• May improve endothelial function and reduce arterial stiffness through pleiotropic effects

Common use

Empagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is also approved to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. Additionally, it is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA Class II–IV), and to reduce the risk of sustained decline in eGFR, 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 in the morning with or without food. Depending on glycemic control and tolerability, 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 hepatic impairment. In patients with eGFR below 20 mL/min/1.73 m², use is not recommended due to reduced efficacy. Tablets should be swallowed whole with water; they should not be split, crushed, or chewed.

Precautions

Monitor renal function before initiation and periodically during treatment. Assess volume status and correct volume depletion before starting therapy. Consider temporary discontinuation during periods of reduced oral intake or fluid loss. Monitor for signs and symptoms of urinary tract infections and genital mycotic infections. Regularly assess glycemic control and adjust concomitant antidiabetic medications as needed to avoid hypoglycemia. Evaluate patients for history of pancreatitis; discontinue if pancreatitis is suspected. Monitor for ketoacidosis even in the presence of normoglycemia. Not recommended during lactation.

Contraindications

History of serious hypersensitivity reaction to empagliflozin or any component of the formulation. Patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Severe renal impairment (eGFR <20 mL/min/1.73 m²), end-stage renal disease, or patients on dialysis. 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, and thirst. Serious but less frequent adverse effects include hypotension, acute kidney injury, ketoacidosis, urosepsis and pyelonephritis, Fournier’s gangrene, bone fractures, and hypersensitivity reactions. Laboratory abnormalities may include increases in hematocrit, low-density lipoprotein cholesterol, serum creatinine, and decreases in eGFR.

Drug interaction

Diuretics may enhance the risk of volume depletion. Insulin and insulin secretagogues may increase the risk of hypoglycemia; dose reduction of these agents may be necessary. Positive urine glucose tests are expected due to mechanism of action; use alternative methods for monitoring glycemic control. No clinically significant interactions observed with metformin, glimepiride, pioglitazone, sitagliptin, warfarin, verapamil, ramipril, or simvastatin.

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, appropriate supportive measures should be instituted. Removal of empagliflozin by hemodialysis has not been studied; however, based on high protein binding, significant removal by dialysis is unlikely. Monitor for signs and symptoms of dehydration, hypotension, and hypoglycemia; treat symptomatically.

Storage

Store at 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 provided for educational purposes only and is not a substitute for 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 or treatment. Do not disregard professional medical advice or delay in seeking it because of something you have read here.

Reviews

Clinical trials including the landmark EMPA-REG OUTCOME trial demonstrated empagliflozin’s robust cardiorenal benefits, with a 38% reduction in cardiovascular death, 35% reduction in hospitalization for heart failure, and 39% reduction in incident or worsening nephropathy. Real-world evidence studies have consistently replicated these findings across diverse populations. The DAPA-HF and EMPEROR-Reduced trials further established its efficacy in heart failure with reduced ejection fraction, while EMPEROR-Preserved extended these benefits to heart failure with preserved ejection fraction. EMPA-KIDNEY confirmed significant renal protective effects in a broad population of patients with chronic kidney disease. Expert consensus guidelines from the American Diabetes Association, European Society of Cardiology, and Kidney Disease: Improving Global Outcomes now recommend SGLT2 inhibitors including empagliflozin as first-line therapy for appropriate patient populations.