Canagliflozin and polypharmacy burden in CKD

Clinicians often hesitate to add drugs to already complex regimens in chronic kidney disease (CKD). This post-hoc analysis of the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial (n=4401, type 2 diabetes and CKD) asked whether medication burden changes the benefits or safety of canagliflozin. Participants took a mean of 8.3 medicines and were grouped as no polypharmacy (0–4 medicines; 14%), polypharmacy (5–9; 55%) and hyperpolypharmacy (≥10; 31%).  

Canagliflozin’s effects on the primary kidney composite (doubling of serum creatinine, kidney failure, or cardiovascular or kidney death) and on cardiovascular outcomes were consistent across all three groups. Safety outcomes were also similar regardless of medication burden (all P-interaction >0.06). Although treatment discontinuation rose with number of medicines taken, it was less frequent with canagliflozin than with placebo in every group. All-cause hospitalisation, heart failure hospitalisation and cardiovascular death increased with medication burden, meaning patients taking the most medicines had the greatest potential absolute benefit from treatment. 

Despite limitations, including the post-hoc design and restriction to people with diabetes, the findings suggest that polypharmacy alone should not stop clinicians starting a sodium–glucose co-transporter 2 (SGLT2) inhibitor when indicated.  

The full article can be read here.