A Post hoc Analysis of the CANVAS Program
January 23, 2025
In this paper from our cardiovascular research team the aim was to investigate type III collagen (COL III) turnover with the help of pharmacodynamic biomarkers in participants from the CANVAS Program.
The biomarkers of COL III formation (PRO-C3/nordicPRO-C3™) and COL III degradation fragments (C3M/nordicC3M™ and CTX-III/nordicCTX-III™) were assessed in baseline and year 3 plasma from patients enrolled in CANVAS, investigating the effect of canagliflozin in participants with type 2 diabetes. The clinical outcomes explored in this study were hospitalization for heart failure, cardiovascular death and all-cause mortality.
The study showed that higher levels of nordicPRO-C3™ and C3M at baseline were associated with a greater incidence of all investigated outcomes, whereas levels of nordicCTX-III™ at baseline were not associated with any of the investigated outcomes.
After treatment with canagliflozin, the levels of nordicPRO-C3™ decreased and levels of CTX-III increased. An increase from baseline to year 3 in nordicPRO-C3™ in the placebo arm was associated with an increased incidence of cardiovascular outcomes, and in all participants was associated with an increased risk of all-cause mortality.
Reflecting a shift in the dynamics of COL3 turnover after the treatment with canagliflozin, nordicPRO-C3™ and nordicCTX-III™ are promising pharmacodynamic tools. In future interventional trials, they can be used to monitor the impact of the canagliflozin treatment and possibly other sodium-glucose co-transporter-2 inhibitors on tissue remodeling.
Article: Association of type III collagen turnover with cardiovascular outcomes and impact with canagliflozin in the CANVAS Program: A post hoc analysis
