Canagliflozin has dose-dependent effect on cardiovascular outcomes in patients with type 2 diabetes

The SGLT2 inhibitor canagliflozin, at a dose of 300 mg daily but not 100 mg, was associated with an improvement in cardiovascular outcomes and all-cause mortality in patients with type 2 diabetes and cardiovascular disease or cardiovascular risk factors, according to data from the CANVAS trial.

The analysis by Dr Elias Elenjickal (McGill University Health Centre, Canada) was based on data from the CANVAS trial, which enrolled patients with type 2 diabetes and randomised them 1:1:1 to either placebo or canagliflozin at 100 mg or 300 mg daily [1,2]. A total of 4,330 patients were included in the analysis, and the primary outcome was a composite of non-fatal myocardial infarction, stroke, or cardiovascular death [1].

Canagliflozin 300 mg versus placebo significantly reduced the primary outcome (HR 0.82; 95% CI 0.68–0.99), while canagliflozin 100 mg led to a numerical improvement (HR 0.95; 95% CI 0.79–1.14). Furthermore, both doses versus placebo improved the composite of doubling of serum creatinine, end-stage kidney disease, or renal death, while only the 300 mg dose improved all-cause mortality. Subgroup analyses showed that canagliflozin had primary outcome improvement in men, but not in women.

Dr Elenjickal concluded that “canagliflozin 300 mg significantly reduced the primary outcome of major adverse cardiac events,” and continued stressing that “a reduction in all-cause mortality was seen only with the 300 mg dose.” While renal benefits were observed with both doses, hospitalisation for heart failure was reduced only in men. “We found that men had a higher cardiovascular burden at baseline,” commented Dr Elenjickal. Finally, he added that there was a similar safety profile with both assessed doses, and that “there seems to be a dose-dependent effect on cardiovascular outcomes and renal endpoint, which is unique for SGLT2 inhibitors for hard clinical endpoints.”

1. Elenjickal EJ, et al. The effect of canagliflozin dose on cardiovascular and renal outcomes in patients with type 2 diabetes and high cardiovascular risk. 62nd ERA Congress, 4–7 June 2025, Vienna, Austria.
2. Neal B, et al. N Engl J Med. 2017;377(7):644-657.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 6 June 20256 June 2025