SGLT2 inhibitors
2 min read
Updated 2026-03-15
Contents
SGLT2 inhibitors
Inhibit SGLT2 in the proximal tubule → glucosuria + natriuresis independent of the loop pathway. The only GDMT class with benefit across all EF ranges. Can start in-hospital (EMPULSE). Do not activate RAAS — a key advantage over loops.
mechanism
Block SGLT2 (proximal tubule S1) → glucosuria (40–80 g/day) + natriuresis. Also reduce proximal Na⁺ reabsorption via NHE3. Restore tubuloglomerular feedback → reduce intraglomerular pressure → renoprotection. Produce interstitial-selective diuresis — reduce oedema while preserving intravascular volume.
dosing
| Agent | Dose | Initiate if eGFR ≥ | Notes |
|---|---|---|---|
| Empagliflozin | 10 mg PO daily | 20 | Continue to dialysis |
| Dapagliflozin | 10 mg PO daily | 20 | Continue to dialysis |
| Canagliflozin | 100–300 mg PO daily | 30 | Less HF data; amputation signal (CANVAS) |
- No titration needed (empagliflozin, dapagliflozin)
- For acute HF: start once SBP > 100 and eGFR ≥ 20 — do not wait until discharge
key points
- The only GDMT with benefit in HFrEF, HFmrEF, and HFpEF
- Benefit is independent of diabetes status — the glycosuric effect is irrelevant for HF/CKD
- Initial eGFR dip (10–15% at 2–4 weeks) is haemodynamic and renoprotective — do not stop
- Euglycaemic DKA: glucose may be normal — check ketones if unwell. Hold 3–4 days pre-op
- Most common adverse effect: genital mycotic infections (5–10%) — treatable, not a reason to stop
sick day rules
Counsel patients to hold SGLT2i during acute illness, 3–4 days before surgery, and if unable to eat/drink. Check ketones if nausea, vomiting, or abdominal pain — even with normal glucose.
adverse effects
- Genital mycotic infections (5–10%) — vulvovaginal candidiasis, balanitis
- Euglycaemic DKA — rare; risk with insulin omission, surgery, acute illness
- UTIs (modest increase)
- Volume depletion (usually mild)
- Fournier gangrene (extremely rare; FDA warning)
- Lower limb amputations — canagliflozin signal (CANVAS); not confirmed as class effect
evidence
- DAPA-HF (2019) — HFrEF: reduced CV death + HF hospitalisation (HR 0.74)
- EMPEROR-Reduced (2020) — HFrEF: reduced CV death + HF hospitalisation (HR 0.75)
- EMPEROR-Preserved (2021) — HFpEF: reduced HF hospitalisation (HR 0.79)
- DELIVER (2022) — HFmrEF/HFpEF: reduced HF events (HR 0.82)
- EMPULSE (2022) — in-hospital initiation: improved composite at 90 days
- DAPA-CKD (2020) — CKD ± diabetes: reduced kidney progression (HR 0.61)
- EMPA-KIDNEY (2023) — CKD ± diabetes: reduced kidney progression (HR 0.72)