Empagliflozin is a highly 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 of the nephron, it promotes glycosuria and offers a unique mechanism of action distinct from other antidiabetic agents. Its 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 appropriate patient populations.

Features

• Selective SGLT2 inhibitor with minimal affinity for SGLT1
• Available in 10 mg and 25 mg oral tablet formulations
• Once-daily dosing, with or without food
• Renal glucose excretion of approximately 64–90 grams per day at therapeutic doses
• Extensive hepatic metabolism via UGT1A3, UGT1A8, UGT1A9, and UGT2B7
• Terminal elimination half-life of approximately 12–13 hours
• Steady-state plasma concentrations reached within 5 days of initiation

Benefits

• Glycemic Control: Reduces HbA1c by 0.5–0.8% on average, with low risk of hypoglycemia when used as monotherapy
• Cardiovascular Risk Reduction: Demonstrates a 14% relative risk reduction in major adverse cardiovascular events (MACE) and a 38% reduction in cardiovascular mortality in high-risk T2DM patients
• Heart Failure Hospitalization Reduction: Lowers risk of hospitalization for heart failure by 35% in both diabetic and non-diabetic populations
• Renoprotective Effects: Slows progression of kidney disease, with a 39% relative risk reduction in worsening nephropathy, end-stage kidney disease, or renal death
• Weight Reduction: Modest weight loss of 2–3 kg observed over 6–12 months due to caloric loss via glycosuria
• Blood Pressure Reduction: Systolic blood pressure reductions of 3–5 mmHg through mild natriuresis and osmotic diuresis

Common use

Empagliflozin is primarily prescribed for adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control. 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 chronic kidney disease in both diabetic and non-diabetic patients, reflecting its pleiotropic effects beyond glucose management.

Dosage and direction

The recommended starting dose is 10 mg once daily, taken orally with or without food. For patients tolerating 10 mg daily who require additional glycemic control, the dose may be increased to 25 mg once daily. In heart failure and chronic kidney disease indications, the 10 mg dose is typically maintained. Dose adjustment is not required based on age, gender, or race. For patients with eGFR below 45 mL/min/1.73m², continued use for heart failure and CKD benefits is recommended, but glycemic efficacy diminishes as renal function declines. Initiation is not recommended when eGFR is below 20 mL/min/1.73m².

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 genital mycotic infections and urinary tract infections. Evaluate patients for history of pancreatitis. Regularly assess hemoglobin/hematocrit as modest increases may occur. Monitor LDL-C and consider lipid management if increases are observed. Use caution in patients with hepatic impairment. Educate patients about the signs and symptoms of ketoacidosis, even in the presence of normal or only mildly elevated blood glucose levels.

Contraindications

History of serious hypersensitivity reaction to empagliflozin or any component of the formulation. Patients with severe renal impairment (eGFR <30 mL/min/1.73m²), end-stage renal disease, or those on dialysis. Concomitant use with other SGLT2 inhibitors is contraindicated. Not recommended during the second and third trimesters of pregnancy. Should not be used for treatment of type 1 diabetes mellitus due to increased risk of diabetic ketoacidosis.

Possible side effects

Most common adverse reactions (≥5% incidence) include urinary tract infections (7.6–9.3%) and female genital mycotic infections (5.4–6.4%). Other reported side effects include increased urination (3.4–3.6%), thirst (2.2–2.5%), and orthostatic hypotension (1.9–2.3%). Less common but serious adverse events include diabetic ketoacidosis (0.1%), acute kidney injury (0.7%), Fournier’s gangrene (<0.1%), and bone fractures (1.6%). Laboratory abnormalities may include increases in serum creatinine, phosphorus, hematocrit, and LDL cholesterol.

Drug interaction

No clinically significant interactions with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, or simvastatin. Diuretics may enhance the potential for volume depletion. Insulin and insulin secretagogues may increase the risk of hypoglycemia, requiring dose adjustment of these agents. UGT inducers (e.g., rifampin) may decrease empagliflozin exposure. No dosage adjustment recommended when coadministered with commonly used medications.

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. However, 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. Patients should be educated to maintain consistent daily dosing to ensure optimal therapeutic effect.

Overdose

In the event of overdose, contact Poison Control or emergency medical services immediately. Symptoms may include severe volume depletion, hypoglycemia (especially when used with other antidiabetic medications), and electrolyte abnormalities. Management should include supportive measures focused on correcting volume depletion and electrolyte imbalances with intravenous fluids. Hemodialysis is unlikely to be effective due to high protein binding (86.2%). Blood glucose should be monitored and treated appropriately if hypoglycemia occurs.

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 tightly closed and out of reach of children and pets. Do not use beyond the expiration date printed on the packaging. Protect from light and excessive humidity. Do not store in bathroom cabinets where moisture levels may fluctuate.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Treatment decisions should be made by qualified healthcare professionals based on individual patient characteristics and current clinical guidelines. The prescribing information should be consulted for complete details regarding indications, dosing, warnings, and precautions. Patients should not initiate or discontinue therapy without consulting their healthcare provider.

Reviews

Clinical trials demonstrate consistent efficacy and safety profiles. The EMPA-REG OUTCOME trial showed significant cardiovascular mortality reduction (38%, p<0.001) and heart failure hospitalization reduction (35%, p<0.002) in high-risk T2DM patients. The EMPEROR-Reduced trial demonstrated 25% risk reduction in cardiovascular death or hospitalization for heart failure in HFrEF patients (p<0.001). EMPA-KIDNEY trial showed 28% risk reduction in kidney disease progression or cardiovascular death in CKD patients (p<0.001). Real-world evidence studies corroborate trial findings, showing sustained benefits in diverse patient populations with generally favorable tolerability.