Canagliflozin
Weight Management
In plain English
Canagliflozin is an FDA-approved diabetes pill that makes the kidneys release extra sugar into the urine, which lowers blood sugar and can cause modest weight loss and lower blood pressure. In people with diabetes it has also been shown to protect the heart and kidneys. Because it increases sugar in the urine, genital yeast and urinary infections are common; dehydration and, rarely, a serious ketoacidosis can occur.
The science
Canagliflozin inhibits sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubule, reducing glucose reabsorption and increasing urinary glucose excretion; this lowers glycemia and modestly reduces weight and blood pressure. In the CANVAS Program (n=10,142 with type 2 diabetes at high cardiovascular risk), canagliflozin reduced the composite of cardiovascular death, nonfatal MI, or nonfatal stroke by 14% and showed favorable renal signals, but with an increased risk of lower-limb amputation. Genital mycotic infections, volume depletion, and euglycemic diabetic ketoacidosis are recognized risks. Use for weight management outside diabetes is off-label.