Empagliflozin (Jardiance) — SGLT2 Inhibitor — Weight & Metabolism
FDA-approved SGLT2 inhibitor with proven cardiovascular and renal benefits beyond glycemic control. Landmark EMPA-REG OUTCOME trial.
Overview
Empagliflozin (Jardiance) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces blood glucose by blocking glucose reabsorption in the proximal tubule of the kidney, causing urinary glucose excretion of approximately 60-80 g/day. FDA-approved in 2014 for type 2 diabetes, empagliflozin gained landmark status with the EMPA-REG OUTCOME trial (2015), which demonstrated a 38% relative risk reduction in cardiovascular death and a 35% reduction in heart failure hospitalization in patients with T2DM and established cardiovascular disease. These results transformed diabetes treatment guidelines, establishing SGLT2 inhibitors as first-line therapy after metformin for patients with cardiovascular disease or heart failure. Subsequently, empagliflozin received FDA approval for heart failure with reduced ejection fraction (EMPEROR-Reduced, 2020) and heart failure with preserved ejection fraction (EMPEROR-Preserved, 2022), regardless of diabetes status. Additional benefits include modest weight loss (2-3 kg), blood pressure reduction (3-4 mmHg systolic), and renal protection. The mechanism of cardiovascular and renal benefit is not fully understood but involves osmotic diuresis, natriuresis, reduced preload, improved cardiac energetics, and tubuloglomerular feedback modulation.
Indications
- FDA-approved: Type 2 diabetes mellitus
- FDA-approved: Heart failure with reduced ejection fraction (HFrEF)
- FDA-approved: Heart failure with preserved ejection fraction (HFpEF)
- FDA-approved: Risk reduction of CV death in T2DM with established CVD
- Off-label: Chronic kidney disease
Mechanism of Action
Inhibits the sodium-glucose cotransporter 2 in the proximal tubule, blocking reabsorption of ~90% of filtered glucose
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Empagliflozin (Jardiance) | 10 mg | Once daily | Standard dose for T2DM and heart failure |
| Empagliflozin | 25 mg | Once daily | Maximum dose for T2DM |
Evidence Grade
GRADE A
Safety & Contraindications
- Genital mycotic infections (yeast infections) — most common side effect (5-10%)
- Urinary tract infections
- Diabetic ketoacidosis (euglycemic DKA — rare but serious; can occur with normal glucose)
- Volume depletion and hypotension — especially in elderly and on diuretics
- Fournier's gangrene (necrotizing fasciitis of perineum) — very rare but FDA warning
- Amputations: no increased risk with empagliflozin (unlike canagliflozin)
- Do not use in type 1 diabetes (DKA risk)
- Reduced efficacy at eGFR < 30 mL/min for glycemic control (still beneficial for HF/CKD)