Meg Jardine, MBBS, PhD: Mediators and Pathways of Canagliflozin's CV Benefit


Results of a new study are diving deeper into potential mediators of the effects of canagliflozin on heart failure and CV death seen in CREDENCE.

A new analysis from an international team of investigators presented at the American Diabetes Association’s (ADA) 80th Scientific Sessions is offering an overview of potential mediators of canagliflozin’s effects on heart failure and cardiovascular death.

Using data from the phase 3 CREDENCE trial, which collected data related to 62 routine clinical biomarkers and vital sign indicators, investigators identified a dozen potential mediators of the effects of canaglifozin in type 2 diabetics with chronic kidney disease.

Led by Meg Jardine, MBBS, PhD, program head of Innovation and Kidney Research at George Institute for Global Health and head of renal trials for George Clinical, investigators designed the analysis to compare hazard ratios for the effect of canagliflozin in unadjusted versus adjusted models for the average post-randomization levels of each of biomarker examined. Of note, for instances when multiple potential mediators represented a single pathway, those with the strongest univariable mediation underwent testing with multivariable models.

In the univariable analyses, 12 biomarkers mediated the effect of canagliflozin on hospitalizations for heart failure and cardiovascular death. Of these 12, 3 were markers of volume or erythropoiesis (hematocrit=24%, hemoglobin=32%; erythrocytes=27%) and 2 were markers of kidney function. The remaining 8 were serum albumin (39%), serum protein (24%), lactate dehydrogenase (13%), systolic blood pressure (10%), urine pH (8%), serum urate (7%), and gamma-glutamyltransferase (4%).

Results of the multivariable model indicated 74% of the impact of canagliflozin on hospitalizations for heart failure and cardiovascular death was associated with the agent’s effect on hemoglobin UACR, serum urate, and systolic blood pressure. In their conclusion, investigators highlighted the results of this study were similar to those in the CANVAS study, which suggests similar mechanisms of benefit in patients at high risk for cardiovascular events and those with a high risk of progressive kidney disease. 

For further insight into the effects of canagliflozin and the results of this study, HCPLive® reached out to Jardine to take part in a special edition ADA 2020 House Call.

This study, “Mediators of the Effects of Canagliflozin (CANA) on Heart Failure (HF) and CV Death in Patients with Type 2 Diabetes (T2D) and Chronic Kidney Disease (CKD),” was presented at ADA 2020.

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