Introduction
Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor approved by the FDA in 2014. It represents a novel class of oral antidiabetic agents that work by promoting glycosuria through inhibition of glucose reabsorption in the proximal tubule of the kidney. Empagliflozin has demonstrated significant cardiovascular and renal benefits beyond glycemic control, making it a valuable therapeutic option in the management of type 2 diabetes and related conditions.
Mechanism of Action
Empagliflozin selectively inhibits sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules. SGLT2 is responsible for approximately 90% of glucose reabsorption from the glomerular filtrate. By blocking this transporter, empagliflozin reduces renal glucose reabsorption, lowers the renal threshold for glucose, and increases urinary glucose excretion. This insulin-independent mechanism results in reduced plasma glucose concentrations, osmotic diuresis, and mild natriuresis.
Indications
- Type 2 Diabetes Mellitus: As an adjunct to diet and exercise to improve glycemic control
- Cardiovascular Risk Reduction: To reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease
- Heart Failure: To reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure
- Chronic Kidney Disease: To reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease
Dosage and Administration
Standard dosing: 10 mg orally once daily in the morning, with or without food Dose escalation: May increase to 25 mg once daily if tolerated and if needed for glycemic control Special populations:- Renal impairment: Not recommended when eGFR <20 mL/min/1.73m²
- Hepatic impairment: No dose adjustment necessary
- Elderly: No dose adjustment required based on age alone
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
- Absorption: Rapidly absorbed with peak plasma concentrations reached in 1.5 hours
- Distribution: Extensive protein binding (86.2%)
- Metabolism: Primarily metabolized via glucuronidation by UGT1A3, UGT1A8, UGT1A9, and UGT2B7
- Elimination: Half-life of approximately 12.4 hours; primarily eliminated via feces (41.2%) and urine (54.4%)
- Steady-state: Achieved after 5 days of repeated dosing
Contraindications
- History of serious hypersensitivity reactions to empagliflozin
- Severe renal impairment (eGFR <30 mL/min/1.73m²), end-stage renal disease, or patients on dialysis
- Concomitant use with other SGLT2 inhibitors
Warnings and Precautions
Ketoacidosis: Reports of ketoacidosis in patients with type 1 and type 2 diabetes Acute Kidney Injury: Cases reported; consider temporary interruption during reduced oral intake Volume Depletion: May cause symptomatic hypotension; assess volume status before initiation Urosepsis and Pyelonephritis: Serious urinary tract infections reported Hypoglycemia: Risk increased when used with insulin or insulin secretagogues Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): Rare but serious cases reported Genital Mycotic Infections: Higher incidence in patients with history of infectionsDrug Interactions
- Diuretics: Increased risk of volume depletion
- Insulin and Insulin Secretagogues: Increased risk of hypoglycemia
- UGT Inducers: Rifampin may decrease empagliflozin concentrations
- Lithium: SGLT2 inhibitors may decrease lithium concentrations
Adverse Effects
Common (>5%):- Genital mycotic infections
- Urinary tract infections
- Increased urination
- Thirst
- Ketoacidosis
- Acute kidney injury
- Volume depletion
- Hypersensitivity reactions
- Fournier's gangrene
- Lower limb amputations (observed with canagliflozin, risk may apply to class)
Monitoring Parameters
- Glycemic control: HbA1c, fasting glucose
- Renal function: Serum creatinine, eGFR at baseline and periodically
- Volume status: Blood pressure, signs/symptoms of volume depletion
- Electrolytes: Potassium, sodium, magnesium
- Ketones: During acute illness or when symptoms suggest ketoacidosis
- Infections: Monitor for signs of urinary tract and genital infections
- Foot exams: Regular examination for sores, ulcers, or infections
Patient Education
- Take medication once daily with or without food
- Maintain adequate hydration to prevent volume depletion
- Recognize symptoms of hypoglycemia (shakiness, sweating, confusion)
- Monitor for signs of urinary tract infections (painful urination, frequency) and genital infections (itching, discharge)
- Seek immediate medical attention for symptoms of ketoacidosis (nausea, vomiting, abdominal pain, fatigue, difficulty breathing)
- Report any skin changes, pain, or tenderness in genital or perineal area
- Continue lifestyle modifications including diet and exercise
- Regular foot care and inspection is important
- Inform all healthcare providers about empagliflozin use, especially before procedures
References
1. FDA Prescribing Information: Jardiance (empagliflozin) tablets 2. Zinman B, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128 3. Wanner C, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016;375(4):323-334 4. Packer M, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424 5. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291 6. Davies MJ, et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. Diabetes Care. 2022;45(11):2753-2786