empagliflozin
Brand: Jardiance
Prototype Drug
Drug Class: antidiabetic
Drug Family: antidiabetic
Subclass: SGLT2 inhibitor
Organ Systems: endocrinecardiovascularrenal
Mechanism of Action
Inhibits SGLT2 in the proximal renal tubule, reducing renal glucose reabsorption and causing glucosuria; glucose-lowering is insulin-independent; also reduces tubular sodium reabsorption (natriuresis), reducing preload and afterload, and has direct cardiac and renal protective effects beyond glycemic control.
sodium-glucose cotransporter 2 (SGLT2)
Indications
- type 2 diabetes mellitus (glycemic control + CV risk reduction)
- heart failure with reduced ejection fraction (HFrEF) — reduces HF hospitalization and CV death
- chronic kidney disease (CKD) — reduces progression
- off-label: heart failure with preserved ejection fraction (HFpEF)
Contraindications
- eGFR <20 mL/min (for CV/HF benefit; no longer specified for T2DM glycemic indication)
- active genital mycotic infections
- type 1 diabetes (risk of DKA without significant hyperglycemia — euglycemic DKA)
Adverse Effects
Common
- genital mycotic infections (yeast infections — most common in women)
- urinary tract infections
- polyuria
- dehydration/orthostatic hypotension
Serious
- euglycemic diabetic ketoacidosis (DKA) — blood glucose may be <250 mg/dL; high anion gap metabolic acidosis
- lower limb amputations (canagliflozin > empagliflozin)
- Fournier's gangrene (necrotizing fasciitis of perineum — rare)
- acute kidney injury (volume depletion)
- urosepsis and pyelonephritis
Pharmacokinetics (ADME)
| Absorption | ~86% oral bioavailability; take with or without food |
| Distribution | Protein binding 86%; Vd ~73 L |
| Metabolism | UGT2B7 and UGT1A3 (glucuronidation); minimal CYP involvement |
| Excretion | Renal (~41% unchanged) and fecal (~41%) |
| Half-life | ~12 hours |
| Onset | 24 hours for glucose lowering; weeks for CV/renal effects |
| Peak | 1.5 hours |
| Duration | 24 hours |
| Protein Binding | 86% |
| Vd | ~73 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| insulin / insulin secretagogues (sulfonylureas) | additive hypoglycemia; reduce insulin/sulfonylurea dose when adding SGLT2i | moderate |
| diuretics | additive volume depletion and hypotension risk | moderate |
Nursing Considerations
- Counsel patients about genital mycotic infections (most common in women with history of candidiasis) — maintain genital hygiene; may require antifungal treatment; drug holiday if recurrent
- Hold SGLT2 inhibitors 3–4 days before surgery or major procedures due to euglycemic DKA risk in fasting patients on insulin; instruct patient to report nausea, vomiting, abdominal pain, and difficult breathing (DKA symptoms)
- Monitor for signs of UTI; obtain urine culture and treat promptly; SGLT2 inhibitors cause glucosuria which predisposes to urinary tract infections
- For HF indication (Jardiance): empagliflozin demonstrated 25% relative risk reduction in CV death/HF hospitalization in EMPA-REG OUTCOME trial; now standard of care in HFrEF per AHA/ACC guidelines
Clinical Pearls
- Euglycemic DKA is the most dangerous and underrecognized SGLT2 inhibitor complication — patients present with DKA symptoms but blood glucose may be only mildly elevated (200–250 mg/dL), leading to missed or delayed diagnosis
- SGLT2 inhibitors have emerged as the most impactful drug class in cardiology and nephrology this decade — they reduce HF hospitalization, CV death, and CKD progression through mechanisms beyond glycemic control (osmotic diuresis, tubuloglomerular feedback, anti-inflammatory effects)
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.