Canagliflozin (Invokana) for Diabetes & Diabetic Kidney Disease — Weight & Metabolism
First FDA-approved SGLT2 inhibitor with proven kidney outcomes from the CREDENCE trial in diabetic nephropathy.
Overview
Canagliflozin was the first SGLT2 inhibitor approved in the US (2013) and the first to demonstrate kidney protection in diabetic nephropathy. The CANVAS Program (n=10,142) showed 14% reduction in cardiovascular events. The landmark CREDENCE trial (n=4,401) was stopped early for efficacy, demonstrating 30% reduction in the kidney composite endpoint (ESKD, doubling of SCr, renal/CV death) with HR 0.70 (95% CI 0.59-0.82) in patients with T2DM and albuminuric CKD. This was the first dedicated kidney outcome trial with an SGLT2 inhibitor. HbA1c reduction of 0.7-1.0% with 100mg dose, additional 0.1-0.2% with 300mg. Dual SGLT2/SGLT1 inhibition (SGLT1 selectivity ratio ~250:1 vs >2500:1 for empagliflozin). PMID: 28605608, 31038479.
Indications
- Type 2 diabetes mellitus as monotherapy or combination therapy
- Diabetic kidney disease: reduction in risk of ESKD, doubling of SCr, renal death, and CV death
- Cardiovascular risk reduction in T2DM with established CVD
- Reduction of heart failure hospitalization risk in T2DM
Mechanism of Action
Chronic hyperglycemia damages glomeruli, causing hyperfiltration, albuminuria, and progressive nephron loss leading to ESKD
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Canagliflozin (Invokana) | 100 mg | Once daily before first meal | Standard dose; recommended for cardiorenal protection |
| Canagliflozin (Invokana) | 300 mg | Once daily before first meal | Higher dose for additional glycemic control if tolerated |
| Canagliflozin (Invokana) | 100 mg | Once daily | CREDENCE trial dose; eGFR >=30 for initiation |
Safety & Contraindications
- FDA-approved since 2013; first SGLT2 inhibitor with dedicated kidney outcome trial
- CANVAS trial showed possible amputation risk signal (HR 1.97); not confirmed in CREDENCE; FDA removed boxed warning in 2020
- Genital mycotic infections: ~10% in women, ~4% in men; treatable with topical antifungals
- Euglycemic DKA risk: same class precautions; hold perioperatively and during acute illness
- Bone fracture risk suggested in CANVAS (not confirmed in CREDENCE); use caution in osteoporosis
- Volume depletion risk: more pronounced at 300mg dose; caution in elderly and those on diuretics