Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
September 4, 2026 · via Europe PMC
Efficacy and safety of canagliflozin are consistent across polypharmacy burden in CKD: the CREDENCE trial.
Yeung EK, Siriwardana A, Buizen L, +13 more, Neuen BL.
AI summary — for doctors, generated from the abstract only
In a post hoc analysis of the CREDENCE trial, canagliflozin's kidney and cardiovascular benefits in patients with type 2 diabetes and CKD were consistent regardless of how many other medications patients were taking, with larger absolute benefits in those with greater medication burden.
What was studied
This post hoc analysis of the CREDENCE trial (4,401 participants with type 2 diabetes and CKD) categorized patients by polypharmacy status (no polypharmacy: 0-4 medicines; polypharmacy: 5-9; hyperpolypharmacy: ≥10) and assessed whether canagliflozin's relative and absolute effects on kidney, cardiovascular, and safety outcomes differed by medication burden.
Key findings
- Among 4,401 participants, 14% had no polypharmacy, 55% had polypharmacy, and 31% had hyperpolypharmacy; mean number of medications was 8.3 (SD 3.77).
- Canagliflozin's effect on kidney and cardiovascular outcomes was consistent across polypharmacy categories, with no significant interaction for safety outcomes (all p-interaction >0.06).
- Treatment discontinuation rates increased with medication burden but were consistently lower with canagliflozin than placebo regardless of polypharmacy status (p-interaction=0.16).
- Because incidence of all-cause hospitalization and heart failure hospitalization/cardiovascular death increased with higher medication burden, the estimated absolute risk reductions with canagliflozin were substantially greater in patients with polypharmacy or hyperpolypharmacy.
Clinical relevance
The findings suggest that polypharmacy alone should not discourage clinicians from adding an SGLT2 inhibitor in patients with type 2 diabetes and CKD for whom it is otherwise indicated, since efficacy and safety appear consistent and absolute benefit may be greater in these more complex patients. This is a post hoc subgroup analysis and was not the trial's original primary comparison.
Who should care
Limitations
As a post hoc analysis, this was not pre-specified as the trial's primary comparison and should be considered hypothesis-supporting rather than definitive; polypharmacy categorization is based on medication counts rather than specific drug-drug interaction risk.
Canagliflozin's kidney and cardiovascular benefits were consistent regardless of polypharmacy burden in CREDENCE, with greater absolute benefit in patients taking more medications, suggesting polypharmacy should not preclude SGLT2 inhibitor use.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background
Polypharmacy in chronic kidney disease (CKD) is substantial. Clinicians and patients are often reluctant to add medications to already complex regimens, partly due to concerns about diminishing efficacy and increased adverse effects. We assessed whether efficacy and safety of canagliflozin is modified by polypharmacy status in patients with type 2 diabetes and CKD.
Methods
We conducted a post-hoc analysis of the CREDENCE trial, which evaluated the effects of canagliflozin on outcomes in patients with type 2 diabetes and CKD. Participants were categorized as no polypharmacy (0-4 medicines), polypharmacy (5-9 medicines), or hyperpolypharmacy (≥10 medicines). We assessed the relative effects of canagliflozin on clinical and safety outcomes by polypharmacy status using Cox proportional hazards models. We assessed absolute benefits using Poisson regression. The primary outcome was a composite of doubling of serum creatinine, kidney failure or death due to cardiovascular or kidney disease.
Results
Among 4401 participants, 612 (14%), 2404 (55%), and 1385 (31%) were categorized as no polypharmacy, polypharmacy and hyperpolypharmacy, respectively. Mean number of medications was 8.3 (SD 3.77). The effect of canagliflozin on kidney and cardiovascular outcomes was consistent irrespective of polypharmacy status, with no interaction observed for safety outcomes (all P-interaction > 0.06). Rates of treatment discontinuation increased with medication burden, but were lower with canagliflozin versus placebo, regardless of polypharmacy status (P-interaction = 0.16). Incidence of all-cause hospitalization, and heart failure hospitalization or cardiovascular death increased with higher medication burden, thus absolute risk reductions were estimated to be substantially greater in patients with polypharmacy and hyperpolypharmacy.
Conclusion
Among patients with type 2 diabetes and CKD, the efficacy and safety of canagliflozin appears consistent regardless of polypharmacy status, with larger estimated absolute reductions in hospitalizations and cardiovascular events in those experiencing polypharmacy or hyperpolypharmacy. These findings suggest that polypharmacy alone should not preclude consideration of SGLT2 inhibitor therapy in patients with CKD and type 2 diabetes for whom treatment is otherwise indicated.
DOI
10.1093/ndt/gfag203
PMID
42695992
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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