canagliflozin
Brand: Invokana
Prototype: empagliflozin
Drug Class: SGLT-2 inhibitor
Drug Family: antidiabetic
Subclass: sodium-glucose cotransporter-2 inhibitor
Organ Systems: endocrinecardiovascularrenal
Mechanism of Action
Inhibits SGLT-2 in the proximal tubule, blocking ~40% of filtered glucose reabsorption, producing glycosuria. At clinical doses also partially inhibits intestinal SGLT-1, reducing postprandial glucose. Additional cardiorenal effects similar to other SGLT-2 inhibitors.
SGLT-2 (proximal tubule)SGLT-1 (at higher doses)
Indications
- type 2 diabetes mellitus
- cardiovascular risk reduction in T2DM with established CVD
- CKD with albuminuria (eGFR 25–75 mL/min)
Contraindications
- type 1 diabetes
- DKA
- eGFR <30 mL/min (T2DM indication)
- dialysis
Adverse Effects
Common
- genital mycotic infections
- UTIs
- polyuria
- volume depletion
Serious
- lower limb amputations (strongest association among SGLT-2 inhibitors; primarily toes)
- DKA (euglycemic)
- acute kidney injury
- Fournier's gangrene
- bone fractures (class effect)
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~65% |
| Distribution | 99% protein bound |
| Metabolism | hepatic glucuronidation (UGT1A9, UGT2B4); CYP3A4 minimal |
| Excretion | fecal (52%) and renal (33%) |
| Half-life | 10.6–13.1 hours |
| Onset | rapid |
| Peak | 1–2 hours |
| Duration | 24 hours |
| Protein Binding | 99% |
| Vd | 83.5 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| rifampin | UGT induction decreases canagliflozin levels by 51% | major |
| digoxin | canagliflozin increases digoxin AUC by 20%; monitor digoxin levels | moderate |
Nursing Considerations
- Assess for peripheral vascular disease, neuropathy, and history of amputation before initiating; counsel about foot care and daily foot inspection.
- CREDENCE trial demonstrated significant reductions in CKD progression and CV events in diabetic nephropathy; ensure indication review.
- Monitor blood pressure and volume status; orthostatic hypotension risk especially in elderly patients on diuretics.
- Instruct patients to promptly report pain, tenderness, or swelling of genitalia or perineum (Fournier's gangrene is rare but life-threatening).
Clinical Pearls
- Canagliflozin has the strongest association with lower limb amputations (primarily toes/metatarsals) among SGLT-2 inhibitors, identified in the CANVAS trial; use with caution in patients with peripheral artery disease or prior amputation.
- The CREDENCE trial established canagliflozin as the first agent to show significant renal protection in diabetic nephropathy since the ACE inhibitor/ARB trials of the 1990s.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.