Empagliflozin
Jardiance · Synjardy · Glyxambi
A diabetes drug now used mostly for reasons other than glucose control. Empagliflozin reduced cardiovascular death in type 2 diabetes in EMPA-REG OUTCOME, reduced heart failure events regardless of ejection fraction in EMPEROR-Reduced and EMPEROR-Preserved, and slowed renal function decline down to eGFR 20 in EMPA-KIDNEY. The glucose-lowering effect diminishes as eGFR falls, but the cardiorenal effect persists — which is the entire point of the drug.
Euglycaemic ketoacidosis is the most dangerous adverse effect: the patient can be severely acidotic with plasma glucose below 14 mmol/l, which means the diagnosis is missed. Check ketones in nausea, abdominal pain, and dyspnoea regardless of glucose level, and pause the drug before major surgery and during acute illness.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Type 2 diabetes | 10 mg × 1, may be increased to 25 mg × 1 | increase to 25 mg only at eGFR ≥ 60 ml/min with insufficient glucose control |
| Chronic heart failure, all ejection fractions | 10 mg × 1 regardless of diabetes status | no titration, no additional effect from 25 mg |
| Chronic kidney disease | 10 mg × 1 | initiate down to eGFR 20 ml/min; continue until dialysis is started |
| Initiation after myocardial infarction or heart failure admission | 10 mg × 1, ideally already during the hospital stay | check volume status and consider reducing the loop diuretic dose |
| Perioperative management | pause 3 days before planned major surgery | restarted when the patient is eating normally and ketones have normalised |
eGFR ≥ 60 ml/min: full dose, 25 mg possible for the diabetes indication. eGFR 45–59 ml/min: 10 mg, diminishing glucose-lowering effect. eGFR 20–44 ml/min: 10 mg for the cardiorenal indication — the glucose-lowering effect is in practice absent. eGFR below 20 ml/min: do not initiate new treatment; ongoing treatment may continue until dialysis begins.
No dose adjustment in mild to moderate hepatic impairment. Not recommended in severe hepatic failure — exposure increases and documentation is insufficient.
Approved from age 10 years in type 2 diabetes: 10 mg × 1, may be increased to 25 mg × 1. No documentation for heart failure or kidney disease in children.
Do not initiate in a patient with type 1 diabetes outside specialist care, and do not miss pausing it before surgery or during acute illness with fasting — that is when euglycaemic ketoacidosis occurs. Also avoid in patients with recurrent genital fungal infections or recurrent urosepsis; in those cases the adverse effects outweigh the benefit.
Pharmacokinetics
- BIOAVAIL.
- Approximately 78 %
- Tmax
- 1,5 hours
- t½
- 12,4 hours
- PROTEIN BINDING
- 86 %
- METABOLISM
- Glucuronidation (UGT2B7, 1A3, 1A8, 1A9)
- EXCRETION
- Renal 54 %, faecal 41 %
- MECHANISM
- Inhibits SGLT2 in the proximal tubule
- ONSET
- glucosuria within hours · cardiorenal effect within weeks