Canagliflozin Side Effects

Reported Canagliflozin side effects

Common effects in trials In four 26-week placebo-controlled trials pooled in the US label, genital fungal infections occurred in 10.6 and 11.6 percent of women taking canagliflozin 100 and 300 mg against 2.8 percent on placebo, and in 4.2 and 3.8 percent of men against 0.7 percent (US prescribing information for Invokana). Urinary tract infections (5.9 and 4.4 against 3.8 percent), increased urination (5.1 and 4.6 against 0.7 percent) and thirst were also more common than with placebo (US prescribing information for Invokana). Lower limb amputation In the CANVAS Program, amputations occurred at 6.3 against 3.4 per 1,000 participant-years with canagliflozin and placebo (hazard ratio 1.97, 95% CI 1.41 to 2.75), mainly at the level of the toe or metatarsal (PMID: 28605608). A secondary analysis of the 187 people with amputations found similar risk at 100 and 300 mg and for ischemic and infective causes, with a previous amputation as the strongest risk factor (hazard ratio 21.31) (PMID: 30868176). The CREDENCE trial found no significant difference in amputation rates (PMID: 30990260). A pooled analysis of the two programs could not explain the difference between them and concluded that the CANVAS finding may have been due to chance, given null results in CREDENCE and in other large SGLT2 inhibitor trials (PMID: 32436638). The current label keeps lower limb amputation as a warning and cites 5.9 against 2.8 events per 1,000 patient-years in CANVAS and 7.5 against 4.2 in CANVAS-R (US prescribing information for Invokana). Bone fracture In the CANVAS Program, fractures occurred at 15.40 against 11.93 per 1,000 patient-years (hazard ratio 1.26, 95% CI 1.04 to 1.52), with a higher risk in CANVAS (hazard ratio 1.55) but not in CANVAS-R (hazard ratio 0.86); the authors could not explain the difference and, given the null CREDENCE result, judged the CANVAS association likely to be a chance finding (PMID: 31399845, PMID: 30990260). The US label keeps a bone fracture warning and notes fractures as early as 12 weeks after the start of treatment in CANVAS (US prescribing information for Invokana). In ITP mice given canagliflozin from 7 to 22 months of age, the femur cortex became thinner in both sexes and cortical bone mineral density fell in males (PMID: 37166526). Ketoacidosis, kidney injury and genital infections The label warns of ketoacidosis (including fatal postmarketing cases in type 2 diabetes), with blood glucose at presentation that may be below 250 mg/dL; of volume depletion, with postmarketing reports of acute kidney injury, some needing hospitalization and dialysis; of genitourinary infections including urosepsis, pyelonephritis and necrotizing fasciitis of the perineum (Fournier's gangrene); of hypoglycemia when combined with insulin or insulin secretagogues; and of hypersensitivity reactions (US prescribing information for Invokana). An FDA review of spontaneous reports identified 55 cases of Fournier's gangrene in people taking SGLT2 inhibitors, the drug class that includes canagliflozin, between 1 March 2013 and 31 January 2019; all needed surgical debridement and 3 died (PMID: 31060053). Female mice in late life (animal data) When the ITP started canagliflozin at 16 months of age, female lifespan fell by 6 percent, and end-of-life pathology showed no clear pattern that explained the sex-specific effects (PMID: 38753230, PMID: 40601216).

When to continue, reduce, or stop Canagliflozin

Canagliflozin contraindications

The label lists a serious hypersensitivity reaction to canagliflozin as a contraindication (US prescribing information for Invokana). In the CANVAS trials, amputation risk was highest in people with a previous amputation, peripheral vascular disease or neuropathy, and lower limb infections, gangrene and diabetic foot ulcers were the most common events leading to amputation (US prescribing information for Invokana; PMID: 30868176). Canagliflozin is not indicated for glycemic control in type 1 diabetes, where it markedly raises the risk of diabetic ketoacidosis, and the label lists reduced calorie intake, a ketogenic diet, acute febrile illness, surgery, volume depletion, alcohol abuse and insulin dose reduction as conditions that can precipitate ketoacidosis (US prescribing information for Invokana). The label does not recommend canagliflozin for glycemic control when eGFR is below 30 mL/min/1.73 m2, and lists impaired kidney function, older age and loop diuretics as factors that raise the risk of volume depletion or low blood pressure (US prescribing information for Invokana). Based on kidney findings in juvenile rats, the label does not recommend canagliflozin during the second and third trimesters of pregnancy or while breastfeeding (US prescribing information for Invokana). Canagliflozin has not been studied in severe hepatic impairment, and the label does not recommend it in that group (US prescribing information for Invokana). The label advises considering factors that contribute to fracture risk, based on the CANVAS fracture finding (US prescribing information for Invokana). For aging use, the lifespan results come from mice, and a late start shortened female mouse lifespan (PMID: 38753230); no human trial has measured an effect of canagliflozin on aging.

Why vendor quality drives Canagliflozin side-effect frequency

Research-compound communities consistently report that adverse-event frequency tracks with source quality. Three reasons: (1) impurity profiles vary by lab (residual synthesis byproducts can trigger reactions); (2) mislabeled mass means actual dose can be 50-150% of stated dose; (3) reconstitution-grade water and capping methodology affect long-term storage stability. COA-verified vendors with published HPLC data minimize all three failure modes. Check a vendor's COA record and Trust Score before you buy.

Canagliflozin side effects FAQ

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