Thread by @brendonneuen

Very proud to present this late breaking clinical trials poster at #KidneyWk:

The largest randomised individual participant data analysis of any #SGLT2 inhibitor to date

🧵 A summary thread:

Why is this analysis important?

1. Composite cardiorenal outcomes are clinically important but have not been consistently reported in trials of SGLT2 inhibitors - Figure from @RangaswJ et al. in @CircAHA #KidneyWk

2. No individual SGLT2 inhibitor trial has enrolled sufficient numbers of participants across the full range of kidney function & albuminuria to robustly assess the magnitude & consistency of cardiorenal benefits across all levels of GFR/albuminuria #KidneyWk

Across the CANVAS Program & CREDENCE trials, there were approximately 14,500 people with type 2 diabetes randomised to canagliflozin or matching placebo, followed for a median of 2.5 years #KidneyWk

Canagliflozin reduced the risk of the primary composite cardiorenal outcome (heart failure, MI, stroke, 2xSCr, kidney failure, CV or renal death) by 23%, with a similar effect on the heart failure renal composite outcome

(Note how early the KM curves separate) #KidneyWk

The relative effect of canagliflozin on the primary cardiorenal outcome *increased* with declining GFR, driven predominantly by MI and stroke

There was some weak evidence of interaction by baseline albuminuria, but benefit present even in those with normoalbuminuria #KidneyWk

Consistent effects across all levels of GFR were observed for the heart failure renal composite outcome, but again, some evidence of greater relative benefit as albuminuria increases #KidneyWk

Perhaps most importantly, absolute risk reductions increase substantially as GFR declines/albuminuria increases

Patients with CKD are those who stand to gain the greatest net clinical benefit from SGLT2 inhibitors

NNT <10 over 2.5 years for the eGFR<45 subgroup #KidneyWk

In summary, canagliflozin reduces the risk of two clinical important cardiorenal outcomes with benefits across a wide range of GFR/albuminuria. People with more advanced CKD stand to gain the greatest net benefit in absolute terms #KidneyWk

Thank you to my colleagues @VladoPerkovic @jardine_meg @HeerspinkHiddo @BruceNeal1 @TheMahaf @DavidCWheeler2 @DCharytan @ArnottClare @AgarwalRajivMD @cpcannon @adeeralevin @GLDiTanna & all participants, investigators & trial teams who made this work possible #KidneyWk