Canagliflozin was the first SGLT2 inhibitor approved in the United States for type 2 diabetes. The CANVAS trial demonstrated cardiovascular benefits, and the CREDENCE trial showed significant renal protective effects. However, canagliflozin carries a unique signal for increased lower-limb amputation risk that is not shared by other SGLT2 inhibitors.
Evidence rating strong. Most-documented uses: lowers hba1c by 0.6–1.0%, cardiovascular event reduction (canvas), significant renal protection (credence: 30% rrr for renal composite). 10 sources indexed (2014–2025), with 1 interaction record on file.
The science
How it works, mechanistically.
Core mechanism
Inhibits sodium-glucose cotransporter 2 in the proximal renal tubule, reducing renal glucose reabsorption and causing glycosuria. At higher doses, canagliflozin also partially inhibits SGLT1 in the intestine, which may contribute to additional postprandial glucose lowering. Promotes osmotic diuresis, natriuresis, weight loss, and blood pressure reduction.6,7
Class
SGLT2 Inhibitor
Dosing
Dosing & protocol.
Common range
100–300 mg once daily before the first meal (as prescribed by your physician)
Recommended form
Oral tablet
Take before the first meal of the day. Can be taken with or without food.
Safety
Full safety detail.
Side effects
Genital mycotic infections
Urinary tract infections
Increased urination
Volume depletion and hypotension
Lower limb amputations (increased risk observed in CANVAS)
Canagliflozin lowers blood glucose through SGLT2 inhibition and chromium improves insulin sensitivity. The combination is usually well tolerated when canagliflozin is the only diabetes drug, but additive glucose-lowering becomes clinically meaningful if insulin or a sulfonylurea is also on board.
Recommendation: If canagliflozin is your only diabetes medication, chromium can be added with home glucose monitoring during the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether the other agent needs a dose reduction first.
Nguyen TN, Yu J, Perkovic V et al.. The Efficacy and Safety of Canagliflozin by Frailty Status in Participants of the CANVAS and CREDENCE Trials. Journal of the American Geriatrics Society. 2025
Yi TW, Smyth B, Di Tanna GL et al.. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2023
Jakher H, Chang TI, Tan M et al.. Canagliflozin review - safety and efficacy profile in patients with T2DM. Diabetes, metabolic syndrome and obesity : targets and therapy. 2019
Elmore LK, Baggett S, Kyle JA et al.. A review of the efficacy and safety of canagliflozin in elderly patients with type 2 diabetes. The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists. 2014
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