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Cardiorenal effects of improving multiple risk factors

Improvements in multiple risk markers – HbA1c, systolic blood pressure, body weight, uACR, uric acid and haemoglobin – are associated with a lower risk of cardiovascular and kidney outcomes.

This post hoc analysis of the CANVAS (Canagliflozin Cardiovascular Assessment Study) programme assessed the degree to which clinically meaningful improvements in six risk markers were associated with the risk of micro- and macrovascular complications in people with type 2 diabetes. The risk marker improvements were as follows:

  • HbA1c reduction of ≥11 mmol/mol (1.0%).
  • Systolic blood pressure (SBP) reduction of ≥10 mmHg.
  • Body weight reduction of ≥3 kg.
  • Urinary albumin:creatinine ratio (uACR) reduction of ≥30%.
  • Uric acid reduction of ≥0.5 mg/dL (30 µmol/L.
  • Haemoglobin increase of ≥10 g/dL.


A total of 9487 people with type 2 diabetes and established or high risk of cardiovascular disease, randomised to canagliflozin or placebo, were included in the analysis. Participants were categorised according to improvements in 0, 1, 2, 3, or ≥4 risk markers over the 26-week study period.

In multivariate analysis, the hazard ratios for these outcomes in people who achieved ≥4 risk marker reductions, compared with those who achieved none, were 0.67 for 3-point major adverse cardiovascular events (MACE), 0.58 for the composite of heart failure or cardiovascular death, and 0.49 for the composite renal endpoint. The trend towards reduced hazard ratios with increasing numbers of risk marker improvements was significant for all three outcomes.

Although participants in the canagliflozin group were more likely to achieve improvements in the selected risk markers, and to have better outcomes in general, the authors point out that almost a third of people in the placebo group achieved clinically relevant improvements in two or more risk markers, highlighting the role of multifactorial treatment as part of optimised care in the CANVAS trials.

The post hoc nature of this analysis means that the results should be interpreted cautiously; however, the authors conclude that improvements in multiple risk markers are associated with a lower risk of cardiovascular and kidney outcomes, and that the results reinforce the value of targeting multiple cardiovascular risk markers in patients with type 2 diabetes.

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