Dapagliflozin
Forxiga · Xigduo · Qtern
An SGLT2 inhibitor whose clinical importance extends well beyond the diabetes indication. DAPA-HF demonstrated reduced cardiovascular death and worsening heart failure with reduced ejection fraction, DELIVER showed equivalent benefit with preserved and mildly reduced EF, and DAPA-CKD demonstrated slowed renal function decline and reduced mortality in chronic kidney disease with albuminuria, with or without diabetes. The dose is the same — 10 mg once daily — for all indications, making this drug unusually straightforward to manage.
Euglycaemic ketoacidosis can occur with plasma glucose below 14 mmol/l and is therefore easily missed. Measure ketones in nausea, abdominal pain, vomiting, or hyperventilation regardless of glucose level, and pause the drug before major surgery and during acute illness with fasting.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Chronic heart failure, all ejection fractions | 10 mg × 1 | no titration; given regardless of diabetes status |
| Chronic kidney disease | 10 mg × 1 | greatest benefit with albuminuria; given with or without diabetes |
| Type 2 diabetes | 10 mg × 1, alone or as add-on | lowers HbA1c approximately 6–8 mmol/mol with preserved renal function |
| Severe hepatic impairment | 5 mg × 1, may be increased to 10 mg if well tolerated | the only situation calling for a lower starting dose |
| Perioperative management | pause 3 days before planned major surgery | restarted when the patient is eating normally and is ketone-free |
No dose adjustment according to renal function — the dose is 10 mg regardless of eGFR. The glucose-lowering effect is reduced at eGFR below 45 ml/min and in practice absent below 30, while the cardiorenal effect persists. Do not initiate new treatment at eGFR below 25 ml/min; ongoing treatment may continue even as eGFR falls below that threshold.
No adjustment in mild to moderate impairment. In severe hepatic failure: start with 5 mg × 1, increase to 10 mg only if well tolerated.
Approved from age 10 years in type 2 diabetes: 10 mg × 1. No documentation for heart failure or kidney disease in children.
The pitfall is initiating the drug in a hypovolaemic patient already on high doses of loop diuretics — the combination causes orthostasis and acute prerenal kidney injury within days. Adjust the diuretic dose simultaneously and check eGFR after two weeks. Avoid in patients with type 1 diabetes outside specialist care and in patients with recurrent genital or urogenital infections.
Pharmacokinetics
- BIOAVAIL.
- Approximately 78 %
- Tmax
- 1–2 hours
- t½
- 12,9 hours
- PROTEIN BINDING
- 91 %
- METABOLISM
- Glucuronidation via UGT1A9
- EXCRETION
- Renal as inactive metabolite (dapagliflozin-3-O-glucuronide)
- MECHANISM
- Inhibits SGLT2 in the proximal tubule
- ONSET
- glucosuria within hours · prognostic effect within weeks