Generic Name

Empagliflozin

Mechanism

• Selective SGLT2 inhibition in the proximal tubule → blocks ~90 % of glucose reabsorption.
• Glucosuria (≈–60 mg/kg/day) decreases plasma glucose independent of insulin.
• Secondary effects: mild natriuresis, osmotic diuresis, ↓ preload/afterload → ↓ blood pressure and weight gain.

Pharmacokinetics

Indications

• Type 2 Diabetes Mellitus (T2DM) – adjunct to diet, exercise, and/or other glucose‑lowering agents (metformin, sulfonylurea, GLP‑1 RA, insulin).
• Heart Failure with Reduced Ejection Fraction (HFrEF) – 2.5‑mg BID improves morbidity/mortality (EMPEROR‑HF).
• Chronic Kidney Disease (CKD) – slows GFR decline; recommended for CKD with/without diabetes (EMPEROR‑Renal).

*Note: Not approved for Type 1 diabetes or pediatric patients.*

Contraindications

• Contraindicated: Severe renal impairment (CrCl <30 mL/min), end‑stage renal disease, active urinary tract infection, diabetic ketoacidosis, hyperosmolar hyperglycemic state.
• Warnings:
• Genital/urinary tract infections – ↑ risk of vulvovaginal candidiasis & UTI.
• Volume depletion – hypotension, dizziness.
• Acute kidney injury – monitor serum creatinine and BUN.
• Hypoglycemia – risk increases when combined with insulin or sulfonylureas.
• Anemia & ketoacidosis – monitor ketones and hemoglobin.
• Pregnancy – avoid, discontinue before conception.

Dosing

• Starting dose: 10 mg daily (preferable 10 mg) or 10 mg twice a day (for heart failure/CKD), taken once daily with or without food.
• Maintenance: 25 mg once daily (or 25 mg BID for heart failure/CKD).
• Titration: Increase to 25 mg after at least 4 weeks if glycemic control inadequate and renal function acceptable.
• Renal adjustment:
• CrCl 30–59 mL/min → 10 mg daily.
• CrCl <30 mL/min → hold; not advised.

Adverse Effects

• Common (<10 %):
• Genital mycotic infections (vulvovaginal candidiasis, balanitis).
• Urinary tract infections.
• Polyuria/polydipsia.
• Mild hypotension, dizziness.
• Headache, nasopharyngitis.
• Serious (≤1 %):
• Ketoacidosis (often normoglycemic).
• Nephrogenic diabetes insipidus → electrolyte imbalance.
• Fournier’s gangrene (rare).
• Hypersensitivity reactions.
• Acute kidney injury.
• Anemia (especially in CKD).

Monitoring

• Baseline & every 3 months:
• eGFR (or serum creatinine).
• HbA1c.
• Serum electrolytes (Na⁺, K⁺).
• Urinalysis for ketones (if symptoms).
• During therapy:
• Blood pressure (especially at initiation).
• Assess for signs of genital/urinary tract infections.
• Weight (baseline → every 4 weeks).

Clinical Pearls

• “Glucose‑insensitive card”: Empagliflozin lowers glucose but remains effective in patients with β‑cell dysfunction; useful when insulin resistance is high.
• HFrEF synergy: Combining empagliflozin with standard HF therapy (ACEi/ARB, β‑blocker) yields additive mortality benefit—start at 10 mg BID; up‑titrate to 25 mg BID once renal function stable.
• CKD benefit independent of diabetes: Empagliflozin slows albuminuria progression by ~30 % even when glycemic control not markedly improved.
• Hypoglycemia mitigation: Use with sulfonylureas cautiously; consider sulfonylurea dose reduction or switch to basal‑bolus insulin titration.
• Pregnancy‑discontinuation window: Stop at least 3 months before conception due to long‑acting metabolites; counsel on contraception.
• Genital infection prophylaxis: Educate patients on perineal hygiene; treat early with topical antifungals; switch to systemic therapy if recurrence.
• Renal dosing nuance: Because 80 % is renal excretion, monitor creatinine within first week after dose change; do not abruptly discontinue if CrCl →30 mL/min—hold therapy, reassess.

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• *All data sourced from FDA prescribing information, EMPA-REG OUTCOME, EMPEROR‑HF & CKD trials, and current KDIGO/ADA guidelines.*